Evaluation of new base-labile 2-(4-nitrophenylsulfonyl) ethoxycarbonyl (Nsc)-amino acids for solid-phase peptide synthesis.
The 2-(4-nitrophenylsulfonyl)ethoxycarbonyl (Nsc) group is a new base-labile protecting group for solid-phase peptide synthesis, completely interchangeable with the fluorenylmethoxycarbonyl (Fmoc) protecting group, but with certain advantages. In this paper, we report a methodology with Nalpha-Nsc-protected amino acids for the synthesis of some melanotropins important to our research, namely, gamma-melanocyte-stimulating hormone (gamma-MSH), its [Nle3]-analogue, and a cyclic alpha-MSH/beta-MSH hybrid. We developed an efficient protocol for the synthesis of the cyclic MSH analogue that yielded this peptide in >98% purity. The gamma-MSH synthesis, which gave problems with both the Boc and Fmoc strategies, yielded the desired peptide by Nsc-chemistry but was accompanied by side products. Finally, the Nle3-gamma-MSH analogue was synthesized more efficiently using the Fmoc strategy, suggesting that Nsc-chemistry might not be the best methodology for certain sequences.
Balse
P M
PM
Department of Chemistry, University of Arizona, Tucson 85721, USA.
Kim
H J
HJ
Han
G
G
Hruby
V J
VJ
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry*; D004220:Disulfides / Q000737:chemistry; D005069:Evaluation Studies as Topic; D005449:Fluorenes / Q000737:chemistry*; D009074:Melanocyte-Stimulating Hormones / Q000138:chemical synthesis / Q000737:chemistry*; D019906:Nuclear Magnetic Resonance, Biomolecular; D010452:Peptide Biosynthesis
D000596:Amino Acids; D004220:Disulfides; D005449:Fluorenes; D009074:Melanocyte-Stimulating Hormones