Comparative study of the neuroprotective and nootropic activities of the carboxylate and amide forms of the HLDF-6 peptide in animal models of Alzheimer's disease.

A comparative study of the neuroprotective and nootropic activities of two pharmaceutical substances, the HLDF-6 peptide (HLDF-6-OH) and its amide form (HLDF-6-NH2), was conducted. The study was performed in male rats using two models of a neurodegenerative disorder. Cognitive deficit in rats was induced by injection of the beta-amyloid fragment 25-35 (βA 25-35) into the giant-cell nucleus basalis of Meynert or by coinjection of βA 25-35 and ibotenic acid into the hippocampus.

Practical, laboratory-scale synthesis of N(in) -formyl tryptophan hydrobromide.

A range of inorganic and organoelement halides was evaluated as acidic promoters of direct N(in) -formylation of tryptophan. In addition to Me3 SiBr, the less expensive PBr3 was found to be highly efficient and was selected for further optimization. A convenient and reproducible synthetic procedure for N(in) -formyltryptophan hydrobromide developed in this way was scaled to 150 mmol and successfully extended to some derivatives of Trp and closely related indoles as detailed in the present paper.

Formation of truncated peptide by-products via sequence-specific formyl group transfer from Trp(For) residues to Nα in the course of Boc-SPPS.

(N(In))-Formyl protective group of tryptophan has been introduced as a base/nucleophile-labile protective group. It has long been known that a free Nα-amino group of the peptide can serve as a nucleophile: an irreversible formyl N(In)  → NH(2) transfer is consistently observed when deformylation is performed last on an otherwise deprotected peptide that possesses free Nα-amino group. Obviously, this particular side reaction should be expected any time free amino group is exposed to Trp(For), but, at the best of our knowledge, has never been reported in the course of Boc-SPPS.

Identification of pentadecapeptide mimicking muramyl peptide.

We used monoclonal antibody, generated against N-acetylglucosaminyl-beta1-4-N-acetylmuramyl-alanyl-D-isoglutamine (GMDP), and phage display libraries of random peptides to select for oligopeptides, that mimic GMDP in their biological activity. Selected phage clones displayed a peptide RVPPRYHAKISPMVN (called RN-peptide) on their surface. This peptide was synthesized.

Effect of zinc and temperature on the conformation of the gamma subunit of retinal phosphodiesterase: a natively unfolded protein.

The cyclic GMP phosphodiesterase gamma-subunit (PDEgamma) was shown to belong to the family of natively unfolded proteins. Increasing temperature transforms the protein into a more ordered (but still relatively disordered) conformation. The C-terminal part of PDEgamma has a high-affinity zinc-binding site (Kd approximately 1 microM), with His75 and His79 being directly involved into the coordination of Zn2+.