Evaluation of new base-labile 2-(4-nitrophenylsulfonyl) ethoxycarbonyl (Nsc)-amino acids for solid-phase peptide synthesis

• Published in: The journal of peptide research 2000-08, Vol.56 (2), p.70-79
• Main Authors: Balse, P M, Kim, H J, Han, G, Hruby, V J
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Amino Acids - chemistry; Disulfides - chemistry; Evaluation Studies as Topic; Fluorenes - chemistry; Melanocyte-Stimulating Hormones - chemical synthesis; Melanocyte-Stimulating Hormones - chemistry; Nuclear Magnetic Resonance, Biomolecular; Peptide Biosynthesis
• ISSN: 1397-002X
• DOI: 10.1034/j.1399-3011.2000.00759.x

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.