Torrey Pines Institute for Molecular Studies

About: Torrey Pines Institute for Molecular Studies is a nonprofit organization based out in San Diego, California, United States. It is known for research contribution in the topics: T cell & Antigen. The organization has 2323 authors who have published 2217 publications receiving 112618 citations.

Specificities of broadly neutralizing anti-HIV-1 sera.

Abstract: PURPOSE OF REVIEW Effective vaccine-elicited immunity against HIV-1 infection will likely require broadly neutralizing antibodies to interrupt the fusion-promoting functions of the viral envelope glycoprotein spikes. Efforts in this area have, however, been fraught with challenges. The handful of existing broadly neutralizing monoclonal antibodies has provided information on some of the virus' sites of vulnerability, fueling a decade of structure-informed vaccine design. The fact that very few bnmAbs have been recovered to date illustrates the poor immunogenicity of these epitopes. Recognizing that progress may require more basic information, there has been a notable shift in the field toward identifying new chinks in HIV-1's armor. These efforts are based on the observation that some infected patients develop exceptionally broad serum neutralizing antibodies responses, a better understanding of which would be valuable for vaccine efforts aimed at eliciting similar specificities. RECENT FINDINGS New mapping methodologies are now providing an appreciation of the incidence of specificities similar to the existing known bnmAbs as well as some intriguing insights into novel specificities. SUMMARY The new information emerging from mapping efforts should help to sharpen efforts to isolate new bnmAbs and moreover, may provide crucial information for the rational design of novel vaccine candidates.

Intravenous ascorbic acid to prevent and treat cancer-associated sepsis?

Abstract: The history of ascorbic acid (AA) and cancer has been marked with controversy. Clinical studies evaluating AA in cancer outcome continue to the present day. However, the wealth of data suggesting that AA may be highly beneficial in addressing cancer-associated inflammation, particularly progression to systemic inflammatory response syndrome (SIRS) and multi organ failure (MOF), has been largely overlooked. Patients with advanced cancer are generally deficient in AA. Once these patients develop septic symptoms, a further decrease in ascorbic acid levels occurs. Given the known role of ascorbate in: a) maintaining endothelial and suppression of inflammatory markers; b) protection from sepsis in animal models; and c) direct antineoplastic effects, we propose the use of ascorbate as an adjuvant to existing modalities in the treatment and prevention of cancer-associated sepsis.

Improving the stability of α-conotoxin AuIB through N-to-C cyclization: the effect of linker length on stability and activity at nicotinic acetylcholine receptors.

Abstract: Modification of α-conotoxin frameworks through cyclization via an oligopeptide linker has previously been shown as an effective strategy for improving in vivo stability. We have extended this strategy by investigating cyclic analogs of α-conotoxin AuIB, a selective α(3)β(4) nicotinic acetylcholine receptor (nAChR) antagonist, to examine a range of oligopeptide linker lengths on the oxidative formation of disulfide bonds, activity at nAChRs, and stability to degradation by chymotrypsin. Upon nondirected random oxidation, the ribbon isomer formed preferentially with the globular isomer occurring as a minor by-product. Therefore, a regioselective disulfide bond forming strategy was used to prepare the cAuIB-2 globular isomer in high yield and purity. The cAuIB-2 globular isomer exhibited a threefold decrease in activity for the α(3)β(4) nAChR compared to wild-type-AuIB, although it was selective for α(3)β(4) over α(7) and α(4)β(2) subtypes. On the other hand, the cAuIB-2 ribbon isomer was shown to be inactive at all three nAChR subtypes. Nonetheless, all of the cyclic analogs were found to be significantly more stable to degradation by chymotrypsin than wild-type AuIB. As such, the cAuIB-2 globular isomer could constitute a useful probe for studying the role of the α(3)β(4) nAChR in a range of in vivo experimental paradigms.

A traceless approach to amide and peptide construction from thioacids and dithiocarbamate-terminal amines

Abstract: A novel and traceless strategy has been devised that allows a coupling of thioacids and dithiocarbamate-terminal amines. This strategy had been assumed to be dependent on the attachment of a functional equivalent of a cysteine side chain in earlier native chemical ligation approaches. This approach enables the traceless removal of CS2 to directly generate the desired amide bond and is compatible with a range of unprotected side chains of amino acid. The ability to produce amide or peptides by a traceless removal of the auxiliary is a significant virtue of the method. Meanwhile, the application of this new peptide-bond-forming reaction to the synthesis of novel endomorphin (EM) derivatives with various binding potencies was realized.

Sequence-ready physical map of the mouse chromosome 16 region with conserved synteny to the human velocardiofacial syndrome region on 22q11.2.

Abstract: Proximal mouse Chromosome (Chr) 16 shows conserved synteny with human Chrs 16, 8, 22, and 3 The mouse Chr 16/human Chr 22 conserved synteny region includes the DiGeorge/Velocardiofacial syndrome region of human Chr 22q112 A physical map of the entire mouse Chr 16/human Chr 22 region of conserved synteny has been constructed to provide a substrate for gene discovery, genomic sequencing, and animal model development A YAC contig was constructed that extends ca 54 Mb from a region of conserved synteny with human Chr 8 at Prkdc through the region conserved with human Chr 3 at DVL3 Sixty-one markers including 37 genes are mapped with average marker spacing of 90 kb Physical distance was determined across the 26-Mb region from D16Mit74 to Hira with YAC fragmentation The central region from D16Jhu28 to Igl-C1 was converted into BAC and PAC clones, further refining the physical map and providing sequence-ready template The gene content and borders of three blocks of conserved linkage between human Chr 22q112 mouse Chr 16 are refined