84000-07-7Relevant articles and documents
Total synthesis of hytramycin V, an antibiotic cyclopeptide
Igarashi, Masayuki,Inaba, Tetsuya,Ishizaki, Yoshimasa,Kigoshi, Hideo,Yoshida, Masahito
supporting information, p. 1922 - 1930 (2021/08/13)
The total synthesis of the piperazic acid-containing antibiotic cyclic peptide, hytramycin V, has been achieved. Unexpected cleavage of the peptide bond was observed during the synthesis of a pentapeptide, we then successfully found that the addition of 2,6-di-tert-butylpyridine (2,6-DTBP) was effective to prevent the cleavage upon acylation with AgCN, leading to a pentapeptide in excellent yield. The synthesis of a hexapeptide, followed by global deprotection of the protecting groups provided a cyclization precursor. Finally, macrolactamization of the precursor using T3Pμ under high-dilution conditions furnished the desired natural product, hytramycin V. The synthesis of the enantiomer of hytramycin V was also achieved, and no difference between the enantiomers was observed in the evaluation of their antibacterial activity against Mycobacterium strains, revealing the fact that the potency of the activity was not dependent on the chirality of the cyclopeptide backbone.
Investigation for the cyclization efficiency of linear tetrapeptides: Synthesis of tentoxin B and dihydrotentoxin
Sato, Ryota,Oyama, Kie,Konno, Hiroyuki
supporting information, p. 6173 - 6181 (2018/09/17)
Investigation of the cyclization efficiency of N-methyl linear tetrapeptides using a molecular modeling study and chemical synthesis is described. The linear peptide with two N-methyl groups, MeAla-Leu-MePhe-Gly, forms γ-turn like conformation with the am
A new GLP-1 analogue with prolonged glucose-lowering activity in vivo via backbone-based modification at the N-terminus
Bai, Xiaohui,Niu, Youhong,Zhu, Jingjing,Yang, An-Qi,Wu, Yan-Fen,Ye, Xin-Shan
, p. 1163 - 1170 (2016/03/01)
Glucagon-like peptide-1 (GLP-1) is an endogenous insulinotropic hormone with wonderful glucose-lowering activity. However, its clinical use in type II diabetes is limited due to its rapid degradation at the N-terminus by dipeptidyl peptidase IV (DPP-IV). Among the N-terminal modifications of GLP-1, backbone-based modification was rarely reported. Herein, we employed two backbone-based strategies to modify the N-terminus of tGLP-1. Firstly, the amide N-methylated analogues 2-6 were designed and synthesized to make a full screening of the N-terminal amide bonds, and the loss of GLP-1 receptor (GLP-1R) activation indicated the importance of amide H-bonds. Secondly, with retaining the N-terminal amide H-bonds, the β-peptide replacement strategy was used and analogues 7-13 were synthesized. By two rounds of screening, analogue 10 was identified. Analogue 10 greatly improved the DPP-IV resistance with maintaining good GLP-1R activation in vitro, and showed approximately a 4-fold prolonged blood glucose-lowering activity in vivo in comparison with tGLP-1. This modification strategy will benefit the development of GLP-1-based anti-diabetic drugs.
