| Title: | Studies on conformational consequences of i to i + 3 side-chain cyclization in model cyclic tetrapeptides |
| Author(s): | Rao MH; Yang W; Joshua H; Becker JM; Naider F; |
| Address: | "Department of Chemistry, College of Staten Island, City University of New York, USA" |
| DOI: | 10.1111/j.1399-3011.1995.tb01057.x |
| ISSN/ISBN: | 0367-8377 (Print) 0367-8377 (Linking) |
| Abstract: | "In an effort to explore the effect of ring size on the biologically active conformation of cyclic analogs of the mating pheromone alpha-factor (WHWLQLKPGQPMY) from Saccharomyces cerevisiae, eight cyclic tetrapeptides corresponding to the KPGQ portion of alpha-factor were synthesized. These N-alpha-acetyl/carboxyl amide terminal cyclic tetrapeptides were prepared on a 4-methylbenzhydrylamine resin using orthogonal Boc, Fmoc, OFm and OtBut protecting groups and HOBt-DIPC accelerated active esters or urethane-protected N-carboxyanhydrides. On-resin cyclization of the side-chain amino and carboxyl groups of the first and fourth residues, respectively, was performed with the BOP reagent to generate lactams containing 14-18 atoms. HF cleavage resulted in two products, the desired cyclic tetrapeptide and a major side product. All peptides were purified to near homogeneity (> 99%) by using reversed-phase HPLC and were characterized by FBMS and 1H NMR. Certain constrained cyclic tetrapeptides appear to be a mixture of isomers at room temperature as evidenced by HPLC and NMR. The major side product has been identified as a cyclo dimer, obtained as a consequence of interchain cyclization on the resin. CD analysis in several solvents gives evidence that some of the cyclic tetrapeptides exist in beta-turn conformations" |
| Keywords: | "Amino Acid Sequence Chromatography, High Pressure Liquid Circular Dichroism Lactams/chemistry Magnetic Resonance Spectroscopy Molecular Sequence Data Oligopeptides/chemical synthesis/*chemistry Peptides/chemical synthesis/*chemistry Peptides, Cyclic/chemi;" |
| Notes: | "MedlineRao, M H Yang, W Joshua, H Becker, J M Naider, F eng GM22086/GM/NIGMS NIH HHS/ GM22087/GM/NIGMS NIH HHS/ Research Support, U.S. Gov't, P.H.S. Denmark 1995/05/01 Int J Pept Protein Res. 1995 May; 45(5):418-29. doi: 10.1111/j.1399-3011.1995.tb01057.x" |
