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Showing papers by "Georgia State University published in 1993"


Journal ArticleDOI
TL;DR: Findings support the social exchange view that POS creates feelings of obligation that contribute to citizenship behaviors.
Abstract: The social exchange view of commitment (R. Eisenberger, R. Huntington, S. Hutchison, & D. Sowa, 1986) suggests that employees' perceptions of the organization's commitment to them (perceived organizational support, or POS) creates feelings of obligation to the employer, which enhances employees' work behavior. The authors addressed the question of whether POS or the more traditional commitment concepts of affective commitment (AC) and continuance commitment (CC) were better predictors of employee behavior (organizational citizenship and impression management). Participants were 383 employees and their managers. Although results showed that both AC and POS were positively related to organizational citizenship and that CC was negatively related to organizationa l citizenship, POS was the best predictor. These findings support the social exchange view that POS creates feelings of obligation that contribute to citizenship behaviors. In addition, CC was unrelated, whereas AC and POS were positively correlated, with some impression management behaviors.

1,419 citations


Journal ArticleDOI
TL;DR: In this article, the authors examined the association between a firm's external environment, corporate entrepreneurship, and financial performance and found that perceived rather than objective-characteristics of the environment significantly influenced entrepreneurship activities.

1,185 citations


Journal ArticleDOI
TL;DR: This paper reviewed past research on the topic of financial institution efficiency, surveys the contributions in this special issue, and suggests how future research on this important topic might proceed, and suggest how future studies on financial institutions efficiency might proceed.
Abstract: This introductory article reviews past research on the topic of financial institution efficiency, surveys the contributions in this special issue, and suggests how future research on this important topic might proceed.

1,016 citations


Journal ArticleDOI
TL;DR: In this paper, the Covin-Slevin model is extended to better capture the nature of entrepreneurial behavior as well as its antecedents and consequences, highlighting several areas where the model should be revised and extended.
Abstract: The study of firm-level entrepreneurship Is fast becoming a central Issue In the literature. Research on the topicshows Increased vitality and rigor. Recently, Covin and Slevin (1991) have suggested an Integrative model that explains the association between a company's entrepreneurial posture and Its external environment, strategy, Internal factors, and organizational performance. This article highlights several areas wherethe Covin-Slevin model should be revised and extended to better capture the nature of entrepreneurial behavior as well as Its antecedents and consequences.

683 citations


Journal ArticleDOI
TL;DR: The procedures and results obtained in developing a scale to measure the multi-dimensional construct of country image imply that constructs used in international marketing research are scalable and that they can meet precise measurement criteria.

661 citations


Journal ArticleDOI
TL;DR: In this paper, the authors show that when the CEO is also chairman of the board, principal-agent conflicts may be exacerbated because of the consolidation of the decision management and the decision control processes.
Abstract: When the CEO is also chairman of the board, principal-agent conflicts may be exacerbated because of the consolidation of the decision management and the decision control processes. Our results suggest that cost efficiency and return on assets are (1) lower for Chairman-CEO banks, (2) positively (negatively or not) related to Nonchairman-CEO (Chairman-CEO) ownership, and (3) unrelated to institutional and large blockholders ownership, and the proportion of inside (outside) directors. These results suggest top management team structure affects performance and internal monitoring devices may not be as effective as envisioned in the literature.

642 citations


Journal ArticleDOI
TL;DR: It is the collective view that the TIP has played, and will continue to play, a pivotal role in elucidation of the function of MEL in the photoperiodic control of seasonal mammalian responses and that the duration of the MEL signal is the critical parameter of the nocturnal secretion profile of the hormone for the phot operable control of several seasonally adaptive responses in mammalian species as diverse as hamsters and sheep.
Abstract: This review summarizes the evidence showing that the duration of the nocturnal secretory profile of pineal melatonin (MEL) is critical for eliciting seasonally appropriate reproductive physiological and behavioral responses in mammals. We review experiments using the timed infusion paradigm (TIP) to deliver MEL either systemically or centrally to pinealectomized hamsters and sheep. In this paradigm, MEL is infused, usually once daily, for a specific number of hours and at a predetermined time of day. This experimental strategy tests most directly those features of the MEL signal that are necessary to trigger photoperiodic responses. The data suggest that the duration of the MEL stimulation is the critical feature of the MEL signal for both inhibitory and stimulatory effects of the hormone on the photoperiodic control of reproductive development in juvenile Siberian hamsters, and for the photoperiodic control of reproductive and metabolic responses in adult Siberian and Syrian hamsters and sheep. The use of the TIP reveals the importance of the frequency of the signal presentation of MEL and suggests the importance of a period of low-to-absent circulating concentrations of the hormone. The TIP also reveals that the characteristics of the MEL signal that regulate male sexual behavior are similar to those that are critical for reproductive and metabolic responses in Syrian hamsters. We summarize the locations of possible functional MEL target sites identified by combining the TIP with traditional brain lesion techniques. Evidence from such studies suggests that the integrity of the suprachiasmatic nucleus (SCN) region in Siberian hamsters and the anterior hypothalamus in Syrian hamsters is necessary for the response to short-day MEL signals. The TIP has been used to deliver MEL to putative target sites for the hormone in the brain of juvenile and adult Siberian hamsters. The results of these preliminary experiments suggest that the regions of specific MEL binding in this species, especially the SCN, are effective sites where MEL may stimulate short-day-type responses. In contrast, results from intracranial application of MEL in sheep suggest the medial basal hypothalamus as a critical site of action. Finally, we also discuss potential applications of the TIP for identification of brain MEL target sites, understanding of other photoperiodic phenomena and responses, and resolution of the cellular/molecular basis underlying the reception and interpretation of MEL signals.(ABSTRACT TRUNCATED AT 400 WORDS)

527 citations


Journal ArticleDOI
TL;DR: It is concluded that a human-like sociocultural environment is an essential component in the development of human- like social-cognitive and imitative learning skills for chimpanzees, and perhaps for human beings as well.
Abstract: In this study we compared the abilities of chimpanzees and human children to imitatively learn novel actions on objects. Of particular interest were possible differences between chimpanzees raised mostly with conspecifics (mother-reared) and chimpanzees raised in a human-like cultural environment (enculturated). Subjects were thus 3 enculturated and 3 mother-reared chimpanzees, along with 8 18-month-old and 8 30-month-old human children. Each subject was tested over a 2-day period with 16 novel objects. The introduction of each object was preceded by a baseline period in which the subject's natural proclivities toward the object were determined. For 12 objects, a human experimenter demonstrated first a simple and then a complex novel action, instructing the subject in each case to "Do what I do" (chimpanzees were prepared for the task behaviorally as well). For the other 4 objects, demonstration of a single action took place on the first day and the subject's opportunity to imitate was delayed until the second day, 48 hours later. Actions that a subject produced in baseline were excluded from further analysis. For each analyzed action, the subject's behavior was scored as to whether it successfully reproduced (1) the end result of the demonstrated action, and (2) the behavioral means used by the demonstrator. Results showed that in immediate imitation the mother-reared chimpanzees were much poorer imitators than the enculturated chimpanzees and the human children, who did not differ from one another. Surprisingly, on the delay trials, the enculturated chimpanzees significantly outperformed the other 3 groups. We conclude from these results that a human-like sociocultural environment is an essential component in the development of human-like social-cognitive and imitative learning skills for chimpanzees, and perhaps for human beings as well.

427 citations


Book
01 Jul 1993
TL;DR: Comparisons of the language comprehension skills of a 2-year-old child and an 8 year-old bonobo who was raised in a language environment similar to that in which children are raised but specifically modified to be appropriate for an ape suggest that the potential for language comprehension preceded the appearance of speech by several million years at minimum.
Abstract: Previous investigations of the linguistic capacities of apes have focused on the ape's ability to produce words, and there has been little concern for comprehension. By contrast, it is increasingly recognized that comprehension precedes production in the language development of normal human children, and it may indeed guide production. It has been demonstrated that some species can process speech sounds categorically in a manner similar to that observed in humans. Consequently, it should be possible for such species to comprehend language if they have the cognitive capacity to understand word-referent relations and syntactic structure. Popular theories of human language acquisition suggest that the ability to process syntactic information is unique to humans and reflects a novel biological adaptation not seen in other animals. The current report addresses this issue through systematic experimental comparisons of the language comprehension skills of a 2-year-old child and an 8 year-old bonobo (Pan paniscus) who was raised in a language environment similar to that in which children are raised but specifically modified to be appropriate for an ape. Both subjects (child and bonobo) were exposed to spoken English and lexigrams from infancy, and neither was trained to comprehend speech. A common caretaker participated in the rearing of both subjects. All language acquisition was through observational learning. Without prior training, subjects were asked to respond to the same 660 novel sentences. All responses were videotaped and scored for accuracy of comprehension of the English language. The results indicated that both subjects comprehended novel requests and simple syntactic devices. The bonobo decoded the syntactic device of word recursion with higher accuracy than the child; however, the child tended to do better than the bonobo on the conjunctive, a structure that places a greater burden on short-term memory. Both subjects performed as well on sentences that required the ability to reverse work order as they did on sentences that did not require this capacity. These results are discussed in light of a model of the evolution of language that suggests that the potential for language comprehension preceded the appearance of speech by several million years at minimum. The onset of speech is linked to the appearance of fully adapted bipedalism, which necessitated reorientation of the laryngeal tract and made closure of the soft palate possible. For the first time, such closure permitted mammals to easily produce sounds that could be interpreted by the mammalian auditory system in a categorical manner. When these sounds were paired with the previously extant capacity to produce vowels, it became possible to form "bounded vowels" or sound units that could readily be discriminated as units by the auditory system. It is suggested that this physical adaptation allowed the extant cognitive capacity of the hominids to embark on a speech-like mode of communication.

426 citations


Journal ArticleDOI
TL;DR: No clear pattern of molecular structure that favors RNA over DNA interactions for intercalators has emerged, and none of the threading intercalator tested to date have shown selective interactions with RNA.
Abstract: The RNA genomes of a number of pathogenic RNA viruses, such as HIV-1, have extensive folded conformations with imperfect A-form duplexes that are essential for virus function and could serve as targets for structure-specific antiviral drugs. As an initial step in the discovery of such drugs, the interactions with RNA of a wide variety of compounds, which are known to bind to DNA in the minor groove, by classical or by threading intercalation, have been evaluated by thermal melting and viscometric analyses. The corresponding sequence RNA and DNA polymers, poly(A).poly(U) and poly(dA).poly(dT), were used as test systems for analysis of RNA binding strength and selectivity. Compounds that bind exclusively in the minor groove in AT sequences of DNA (e.g., netropsin, distamycin, and a zinc porphyrin derivative) do not have significant interactions with RNA. Compounds that bind in the minor grove in AT sequences of DNA but have other favorable interactions in GC sequences of DNA (e.q., Hoechst 33258, DAPI, and other aromatic diamidines) can have very strong RNA interactions. A group of classical intercalators and a group of intercalators with unfused aromatic ring systems contain compounds that intercalate and have strong interactions with RNA. At this time, no clear pattern of molecular structure that favors RNA over DNA interactions for intercalators has emerged. Compounds that bind to DNA by threading intercalation generally bind to RNA by the same mode, but none of the threading intercalators tested to date have shown selective interactions with RNA.

392 citations


Book
01 Jan 1993
TL;DR: In this article, the idea of cultures of letters and literature in Antebellum America are discussed. But the focus is on the reading of regions rather than the authorship of the authors.
Abstract: Acknowledgments Introduction: On the Idea of Cultures of Letters 1: Sparing the Rod: Discipline and Fiction in Antebellum America 2: Veiled Ladies: Toward a History of Antebellum Entertainment 3: Starting Out in the 1860s: Alcott, Authorship, and the Postbellum Literary Field 4: The Reading of Regions For a History of Literary Access The Reading of Regions: A Study in the Social Life of Forms 5: Jewett, Regionalism, and Writing as Women's Work 6: "Why Could Not a Colored Man?": Chesnutt and the Transaction of Authorship Notes Index

Journal ArticleDOI
TL;DR: Booth et al. as discussed by the authors examined the relationship of testosterone to tendencies to marry and divorce, and to the quality of marriage, of a large representative sample of men, and found that men producing more testosterone are less likely to marry, and more likely to divorce.
Abstract: We examine the relationship of testosterone to tendencies to marry and divorce, and to the quality of marriage, of a large representative sample of men. The analysis shows that men producing more testosterone are less likely to marry and more likely to divorce. Once married they are more likely to leave home because of troubled marital relations, extramarital sex, hitting or throwing things at their spouses, and experiencing a lower quality of marital interaction. Sociological models that might be informed by thisfinding are examined, and its implications for subsequent research are discussed. Studies of the relation between testosterone and marital relations have focused on coital frequency but little else. For example, Morris et al. (1987) showed that female testosterone is related to increases in sexual intercourse. One exception to this focus of testosterone studies is a study by Julian and McKenry (1989) of 39 middle-aged men which showed that testosterone and marital happiness have a negative relationship. Despite the paucity of research, there are important reasons to examine the relation between testosterone and marriage in more detail. Because testosterone has consistent and moderately strong links with aggression (see Meyer-Bahlburg 1981 for summary), dominance (Gray, Jackson & McKinlay 1991), sensation seeking (Daitzman & Zuckerman 1980), depressed occupational achievement (Dabbs 1992), and antisocial behavior such as fighting, nontraffic arrests, and drug use (Dabbs & Morris 1990), it would appear that elevated testosterone has the potential to affect marriages adversely. The purpose of the investigation reported here is to examine the relation between * We are indebted to Paul Amato, Lynn White, Harriet Presser, Philip Morgan, and David Johnson for their comments on an early version of this manuscript. A draft of this article was presented at the Population Association of America meeting in May, 1992. This research was supported in part by grantMMH442525from theAntisocial and Violent Behavior Branch of the National Institute of Mental Health, and the Population Research Institute, Pennsylvania State University, with core support from the National Institute of Child Health and Human Development grant 1-HD28263. The data was originally gathered as part of the Vietnam military experience study, conducted by the Centers for Disease Control, U.S. Public Health Service, under a cooperative agreement with the Veterans Administration. Direct correspondence to Alan Booth, Sociology Department, Pennsylvania State University, University Park, PA

Journal ArticleDOI
TL;DR: A long-term collaborative investigation between palaeolithic archaeologists and cognitive psychologists has focused upon the stone tool-making and tool-using abilities of a captive bonobo (Pan paniscus).


Journal ArticleDOI
TL;DR: Reaching in the light developed in parallel with reaching in the dark, suggesting that visual guidance of the hand is not necessary to achieve object contact either at the onset of successful reaching or in the succeeding weeks.
Abstract: The issue examined was whether infants require sight of their hand when first beginning to reach for, contact, and grasp objects. 7 infants were repeatedly tested between 6 and 25 weeks of age. Each session consisted of 8 trials of objects presented in the light and 8 trials of glowing or sounding objects in complete darkness. Infants first contacted the object in both conditions at comparable ages (mean age for light, 12.3 weeks, and for dark, 11.9 weeks). Infants first grasped the object in the light at 16.0 weeks and in the dark at 14.7 weeks, a nonsignificant difference. Once contact was observed, infants continued to touch and grasp the objects in both light and dark throughout all sessions. Because infants could not see their hand or arm in the dark, their early success in contacting the glowing and sounding objects indicates that proprioceptive cues, not sight of the limb, guided their early reaching. Reaching in the light developed in parallel with reaching in the dark, suggesting that visual guidance of the hand is not necessary to achieve object contact either at the onset of successful reaching or in the succeeding weeks.

Journal ArticleDOI
TL;DR: In this article, the authors reviewed the research on the impostor phenomenon, an experience of feeling incompetent and of having deceived others about one's abilities, and found that imposter feelings are associated with such characteristics as introversion, trait anxiety, a need to look smart to others, a propensity to shame, and a conflictual and non-supportive family background.
Abstract: Research on the impostor phenomenon, an experience of feeling incompetent and of having deceived others about one's abilities, is reviewed. Impostor feelings are shown to be associated with such characteristics as introversion, trait anxiety, a need to look smart to others, a propensity to shame, and a conflictual and non-supportive family background. The findings are discussed in terms of self psychological theory, with the impostor phenomenon seen as a result of seeking self-esteem by trying to live up to an idealized image to compensate for feelings of insecurity and self-doubt. Therapeutic approaches drawing on self psychology and cognitive therapy are suggested.

Journal ArticleDOI
TL;DR: In this paper, a large degree of persistent inefficiency seems to exist among sample firms, the inefficiencies relate to some internal or external monitoring, and rent-seeking may be occurring.
Abstract: Using six years of data, 1985–1990, we estimate hybrid translog cost functions for 561 life insurers. We examine the resulting residuals to determine the relative efficiency of insurers in the sample. We then test the residuals to see if they are related to so-called X-efficiencies because of internal and external monitoring, or to other factors related to rent-seeking. Results show a large degree of persistent inefficiency seems to exist among sample firms, the inefficiencies relate to some internal or external monitoring, and rent-seeking may be occurring.

Journal ArticleDOI
TL;DR: The results indicate that widowhood changed the social environment of subjects, altering the social meaning that eating held for them and producing negative effects on eating behaviors and nutrient intakes.
Abstract: The purpose of this study was to identify the effects of recent widowhood on nutritional behaviors. Fifty recently widowed persons over the age of 60 and 50 married subjects of similar age were interviewed on eating behaviors, focusing on changes since widowhood or within 2 years for the married persons. Widowed subjects completed the Grief Resolution Index, and all subjects recorded dietary intake for 3 days. Data were analyzed using nutrient analysis, correlation coefficients, chi square analysis, and t-tests. The results indicate that widowhood changed the social environment of our subjects, altering the social meaning that eating held for them and producing negative effects on eating behaviors and nutrient intakes.

Journal ArticleDOI
TL;DR: In this article, a dyadic discussion of two socio-moral dilemmas was conducted with 8-year-old females with either their mother or their best friend, and it was found that the consequence of a rejected solution discussion often is the focal's proposal of a more acceptable solution.
Abstract: The present study sought to characterize the mechanism of cognitive change during peer interaction. Forty-eight focal subjects (8-year-old females) were paired with either their mother or their best friend for dyadic discussion of two socio-moral dilemmas. The focal subjects were pretested and posttested to assess any change in their socio-moral reasoning. The hypothesis tested was that subjects cooperatively co-construct solutions to dilemmas; therefore, the discussions regarding solutions they eventually accept, as opposed to those they reject, will be positively related to posttest performance. Contrary to expectations, it was discovered that only the discussion of rejected solutions has a significant relation to cognitive outcome. Close analysis revealed that the consequence of a rejected solution discussion often is the focal's proposal of a more acceptable solution, and this also has a strong relation to outcome. A new conceptualization of collaboration is proposed, one that focuses on the importance of dyadic consideration of multiple perspectives. The consequence of such consideration is both critical analysis of ideas (socio-cognitive conflict) and co-construction of new understanding (cooperation).

Journal ArticleDOI
01 Jun 1993-Virology
TL;DR: The apparently complete sequence of the RNA genome of the neurovirulent isolate of lactate dehydrogenase-elevating virus (LDV-C) has been determined and three cleavage sites in the ORF 1a polyprotein were predicted for the chymotrypsin-like protease and tentatively delimit the mature nonstructural proteins of LDV.

Journal ArticleDOI
TL;DR: The authors explored one mechanism through which acute disaster stress (injury, life threat, property damage, loss) may produce lasting psychological distress (depression, anxiety, somatization, hostility).
Abstract: This study explored one mechanism through which acute disaster stress (injury, life threat, property damage, loss) may produce lasting psychological distress (depression, anxiety, somatization, hostility). More specifically, the study examined the mediating roles of seven domains of chronic stress (marital, parental, filial, financial, occupational, ecological, physical) within a sample of 930 disaster victims and controls. The results provided strong support for the hypothesis that chronic stress mediates the long-term effects of acute disaster stress on psychological distress. The main effects of loss, though limited in strength, were completely explained by victims’ higher financial, marital, filial, and physical stress. The effects of injury, though quite strong, were largely mediated by these same domains of chronic stress. Likewise, the effects of life threat were largely mediated by all these domains plus ecological stress. A mediational model was not appropriate for understanding the consequences of property damage because it did not exhibit a main effect on psychological distress.

Journal ArticleDOI
TL;DR: This study compared the scores of independently identified impostors and nonimpostors on two instruments designed to measure the IP: Harvey's I-P Scale and Clance's IP Scale and suggests that Clance’s scale may be the more sensitive and reliable instrument.
Abstract: Many of the discrepancies reported to date in empirical investigations of the impostor phenomenon (IP) may be due in part to (a) the use of different methods for identifying individuals suffering from this syndrome (impostors), (b) the common use of a median split procedure to classify subjects and (c) the fact that subjects in many studies were drawn from impostor-prone samples. In this study, we compared the scores of independently identified impostors and nonimpostors on two instruments designed to measure the IP: Harvey's I-P Scale and Clance's IP Scale. The results suggest that Clance's scale may be the more sensitive and reliable instrument. Cutoff score suggestions for both instruments are offered.

Journal ArticleDOI
TL;DR: The results indicate that not only body size but also the pattern and amounts of nutrients ingested by humans in natural environments are strongly influenced by the immediate environment and heredity, but not at all by the familial environment.

Journal ArticleDOI
TL;DR: Ingestion of noncaloric beverages, diet sodas, and coffee or tea, were associated with low overall intakes but were not found to influence the amount eaten over the course of the day or in individual meals.

Journal ArticleDOI
TL;DR: There is a significant gulf between the clinical diagnosis of children with specific language impairment and more standardized operational criteria, and it is suggested that the global concept of a "specific language impairment" may not be a useful concept for either clinical or research activities.
Abstract: This paper reports on the results of a large multicenter project designed to develop an empirically based classification of preschool children with language impairments. A clinically selected popul...

Journal ArticleDOI
TL;DR: In this article, the authors assess whether age influenced one's vulnerability to post-disaster stress and evaluate four different perspectives on disaster recovery that have been previously used to explain age differences.
Abstract: At 12, 18, and 24 months after Hurricane Hugo, 831 adults were interviewed regarding their disaster-related stressors and present psychological state. The study's purposes were to assess whether age influenced one's vulnerability to postdisaster stress and to evaluate four different perspectives on disaster recovery that have been previously used to explain age differences. Regression analyses demonstrated that disaster exposure had substantial and pervasive psychological effects. The analyses also revealed a curvilinear interaction between disaster exposure and age. Younger people exhibited the most distress in the absence of disaster, but middle-aged people did so in its presence. Differential exposure, resources, and inoculation all failed to explain these differences, however, the burden perspective had considerable explanatory power. Language: en

Journal ArticleDOI
TL;DR: In this paper, organizational stories are used to study often unstated and perhaps unconscious codes for resolving conflicts, approaching decision-making, determining perceptions of positive and negative organizational forces, guiding role behavior, and the like.
Abstract: An important aspect of corporate culture is its ability to influence relationship dynamics. This article examines how organizational stories can be used to study often unstated and perhaps unconscious codes for resolving conflicts, approaching decision-making, determining perceptions of positive and negative organizational forces, guiding role behavior, and the like. Stories are also defined, prior research is described, and the advantages and disadvantages in using this technique are discussed. We explain how our methodology can uncover comparative relationship patterns for human resource development professionals and business leaders in Fortune 500 companies.

Journal ArticleDOI
TL;DR: The results show that transvestite prostitutes are a heterogenous population and distinct from nontransvestite prostitute; specific outreach is thus needed to address the sexual and drug-use-related HIV risk behaviors of transvestITE prostitutes.
Abstract: Human immunodeficiency virus (HIV)-1, syphilis, and hepatitis B prevalence and associated risk factors were assessed among male transvestite prostitutes. Structured street-level interviews were conducted with 53 respondents in Atlanta, Ga, from July 1990 through July 1991. Test results from serum samples revealed that 68% were seropositive for HIV-1, 81% had seromarkers for syphilis, and 80% had seromarkers for hepatitis B. Univariate logistic regression analysis indicated that seromarkers for syphilis and Black race were the primary factors associated with HIV-1 infection. The results show that transvestite prostitutes are a heterogenous population and distinct from nontransvestite prostitutes; specific outreach is thus needed. Targeted interventions should address the sexual and drug-use-related HIV risk behaviors of transvestite prostitutes.

Journal ArticleDOI
TL;DR: In this paper, the authors present a model for the cognitive group and the strategic group, which uses both concepts as tools in framing strategy research, and propose a new model for intra-industry structure.
Abstract: Alternative conceptualizations of competitive groups have been developed in the strategic management literature, namely, the ‘strategic group’and the ‘cognitive group’. These two views each have their own paradigm base and are often seen as incompatible explanations of intra-industry structure. This article analyses these two views and presents a model for each. It then goes on to develop an integrated model which uses both concepts as tools in framing strategy research. Propositions about the new model are also presented.

Journal ArticleDOI
TL;DR: Spectral changes and energy-transfer results indicate that the naphthyl compound and related derivatives bind to the triplex by intercalation.(ABSTRACT TRUNCATED at 250 WORDS)
Abstract: Triple-helical structures involving the interaction of an oligonucleotide third strand with a duplex nucleic acid sequence have recently gained attention as a therapeutic strategy in the "antigene" approach [cf. Helene, C. (1991) Eur. J. Cancer 27, 1466-1471]. This method utilizes the triple helix formed from the cellular duplex and an added third strand to directly regulate the activity of a selected gene. The limited stability of nucleic acid triple-helical interactions, particularly if the third strand has backbone modifications such as methylphosphonate or phosphorothioate substitutions, is a limiting condition for the use of this approach. We have designed and synthesized compounds, on the basis of the following three criteria, that we feel should provide selective interactions and significant stabilization of triplexes: appropriate aromatic surface area for stacking with triplex bases in an intercalation complex, positive charge, and limited torsional freedom in the aromatic system to match the propeller twist of the triple-base interactions in the triplex. A series of quinoline derivatives with an alkylamine side chain at the 4-position and with different aryl substituents at the 2-position has been synthesized as our first compounds. A 2-naphthyl derivative provides significant and selective stabilization of the triplex. In a 0.2 M NaCl buffer, the naphthyl derivative increased the Tm for the triplex (triplex to duplex and third strand transition) by approximately 30 degrees C more than the Tm increase for the duplex (duplex to single strands transition). Spectral changes and energy-transfer results indicate that the naphthyl compound and related derivatives bind to the triplex by intercalation.(ABSTRACT TRUNCATED AT 250 WORDS)