Journal ArticleDOI
An all D-amino acid opioid peptide with central analgesic activity from a combinatorial library
Colette T. Dooley,N N Chung,Brian C. Wilkes,Peter W. Schiller,Jean M. Bidlack,Gavril W. Pasternak,Richard A. Houghten +6 more
TLDR
Simulations using molecular dynamics showed that three amino acid moieties have the same spatial orientation as the corresponding pharmacophoric groups of the opioid peptide PLO17, demonstrating that this peptide may cross the blood-brain barrier.Abstract:
A synthetic combinatorial library containing 52,128,400 D-amino acid hexapeptides was used to identify a ligand for the mu opioid receptor. The peptide, Ac-rfwink-NH2, bears no resemblance to any known opioid peptide. Simulations using molecular dynamics, however, showed that three amino acid moieties have the same spatial orientation as the corresponding pharmacophoric groups of the opioid peptide PLO17. Ac-rfwink-NH2 was shown to be a potent agonist at the mu receptor and induced long-lasting analgesia in mice. Analgesia produced by intraperitoneally administered Ac-rfwink-NH2 was blocked by intracerebroventricular administration of naloxone, demonstrating that this peptide may cross the blood-brain barrier.read more
Citations
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Synthesis and Applications of Small Molecule Libraries.
TL;DR: Thompson et al. as mentioned in this paper developed a method for the generation of large combinatorial libraries of peptides and oligonucleotides that are then screened against a receptor or enzyme to identify high affinity ligands or potent inhibitors, respectively.
Journal ArticleDOI
Combinatorial synthesis : the design of compound libraries and their application to drug discovery
Journal ArticleDOI
The Current Status of Heterocyclic Combinatorial Libraries.
Journal ArticleDOI
Neuropeptides--an overview
Tomas Hökfelt,Christian Broberger,Zhi-Qing David Xu,Valeriy Sergeyev,Ruud Ubink,Margarita Diez +5 more
TL;DR: It seems that peptides may play a role particularly when the nervous system is stressed, challenged or afflicted by disease, and that peptidergic systems may, therefore, be targets for novel therapeutic strategies.
Journal ArticleDOI
Identification of D-peptide ligands through mirror-image phage display
Ton N. Schumacher,Lorenz M. Mayr,Daniel L. Minor,Michael A. Milhollen,Michael Burgess,Peter S. Kim +5 more
TL;DR: The value of this approach was demonstrated by the identification of a cyclic D-peptide that interacts with the Src homology 3 domain of c-Src, and nuclear magnetic resonance studies indicate that the binding site for this D- peptide partially overlaps the site for the physiological ligands of this domain.
References
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Journal ArticleDOI
General method for the rapid solid-phase synthesis of large numbers of peptides: specificity of antigen-antibody interaction at the level of individual amino acids
TL;DR: Through examination of the binding of these analogs to monoclonal antibodies raised against residues 75-110 of HA1, it was found that a single amino acid, aspartic acid at position 101, is of unique importance to the interaction.
Journal ArticleDOI
Generation and use of synthetic peptide combinatorial libraries for basic research and drug discovery
Richard A. Houghten,Clemencia Pinilla,Sylvie E. Blondelle,Jon R. Appel,Colette T. Dooley,Julio H. Cuervo +5 more
TL;DR: The precise identification of an antigenic determinant recognized by a monoclonal antibody as well as the straightforward development of new potent antimicrobial peptides are presented.
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Dynorphin is a specific endogenous ligand of the kappa opioid receptor.
TL;DR: In the guinea pig ileum myenteric plexus--longitudinal muscle preparation, dynorphin-(1--13) and the prototypical kappa agonist ethylketocyclazocine had equally poor sensitivity to naloxone antagonism and showed selective cross protection in receptor inactivation experiments with the alkylating antagonist beta-chlornaltrexamine.
Journal Article
The use of synthetic peptide combinatorial libraries for the identification of bioactive peptides.
Richard A. Houghten,Appel,Sylvie E. Blondelle,Julio H. Cuervo,Colette T. Dooley,Clemencia Pinilla +5 more
TL;DR: Examples are presented in which an SPCL, composed in total of 52,128,400 acetylated hexa-peptides, is used along with an iterative selection process to precisely identify the antigenic determinant of a peptide recognized by a monoclonal antibody using competitive enzyme-linked immunosorbent assay.
Journal Article
Kappa opiate receptor multiplicity: evidence for two U50,488-sensitive kappa 1 subtypes and a novel kappa 3 subtype.
TL;DR: Competition studies with both alpha-neoendorphin and dynorphin B together suggest that both compounds label the same site with high affinity, whereas Classical kappa opiates and dynoirin A have high affinity for both subtypes whereas dynorphIn B and alpha-Neo endorphin label kappa 1b over 50-fold more potently than kappa 2a sites.