N-Methyl-phenacyloxycarbamidomethyl (Pocam) group: a novel thiol protecting group for solid-phase peptide synthesis and peptide condensation reactions

Abstract

In the so-called thioester method for the condensation of peptide segments, protecting groups for amino and thiol groups are required for chemoselective ligation. In this study, we developed a novel thiol protecting group, N-methyl-phenacyloxycarbamidomethyl (Pocam). We used it for protection of cysteine side chains, and synthesized Pocam-containing peptides and peptide thioesters. These were condensed by the thioester method. After the condensation reaction, Pocam groups were cleaved by Zn/AcOH treatment. At the same time, the azido group, which was used for the protection of lysine side chains, was also converted to an amino group, demonstrating that this protecting group strategy simplified the deprotecting reaction after the peptide condensation reaction to only one step.

Chemical synthesis of the crustacean insulin‐like peptide with four disulfide bonds

“…Cys 11 (Bu t ), Cys29 (Acm), Cys39 (MeOBn)-A chainThe peptide chain was elongated using the remaining half of protected peptide resin with A chain (13-42) sequence described above by the DCC-HOBt method. After the chain assembly, H-Gln (Trt)-Val-Gly-Arg (Pbf)-Lys (Boc)-Thr (Bu t )-Leu-Arg (Pbf)-Glu (OBu t )-Glu (OBu t )-Cys (Bu t )-Cys (Trt)-Gly-Asn (Trt)-Thr (Bu t )-Pro-Phe-Arg (Pbf)-Pro-Cys (Trt)-Thr (Bu t )-Tyr (Bu t )-Glu (OBu t )-Glu (OBu t )-Val-Ala-Glu (OBu t )-Tyr (Bu t )-Cys (Acm)-Glu (OBu t )-Vla-Leu-His (Trt)-Asp (OBu t )-Glu (OBu t )-…”

Chemical synthesis of the S‐linked glycopeptide, sublancin

“…Peptide 6 was dissolved in distilled water, and the solution was added dropwise to an iodine/CH 3 OH solution containing HCl. Unexpectedly, the reaction proceeded slower than the usual cases and did not finish within 1 h at room temperature. So, we carried out this reaction at 40 °C.…”

“…Peptide 6 was dissolved in distilled water, and the solution was added dropwise to an iodine/CH 3 OH solution containing HCl. Unexpectedly, the reaction proceeded slower than the usual cases [9,10] and did not finish within 1 h at room temperature. So, we carried out this reaction at 40 C. The reaction was almost complete within 1 h without significant side reaction, and the desired product, sublancin 1, was obtained by RP-HPLC purification in 20% yield.…”

Disulfide Formation Strategies in Peptide Synthesis

“…[52] The group was developed as a general Cys protecting group for use in conjunction with the condensation reactions of the thioester method. [52] The group was developed as a general Cys protecting group for use in conjunction with the condensation reactions of the thioester method.…”