A General Approach to Optically Pure, α-Methyl Non-Natural Amino Acids: Enabling Unique Peptides as Drug Candidates

被引：1

作者：

Passley, Kyle D. ^{[1
]}

Ruble, J. Craig ^{[2
]}

Kerr, Mark S. ^{[3
]}

Organ, Michael G. ^{[1
]}

机构：

[1] Univ Ottawa, Ctr Catalysis Res & Innovat CCRI, Dept Chem & Biomol Sci, Ottawa, ON K1N 6N5, Canada

[2] Eli Lilly & Co, Lilly Corp Ctr, Discovery Chem Res & Technol, Indianapolis, IN 46285 USA

[3] Eli Lilly & Co, Lilly Corp Ctr, Synthet Mol Design & Dev, Indianapolis, IN 46285 USA

来源：

JOURNAL OF ORGANIC CHEMISTRY | 2024年 / 89卷 / 05期

基金：

加拿大自然科学与工程研究理事会;

关键词：

REAGENTS; BASE;

D O I：

10.1021/acs.joc.3c02677

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

An alpha-methyl, non-natural amino acid (NNAA) building block equipped with an alkyl halide tail that could be readily transformed into an organozinc was prepared. This single organometallic was cross-coupled to an array of heterocyclic electrophiles using the Pd-PEPPSI-IHept(Cl) catalyst to produce a wide selection of optically pure alpha-methyl NNAAs. With these in hand, non-natural peptides are being produced for evaluation in a variety of therapeutic areas in drug discovery.

引用

页码：3211 / 3213

页数：3

共 25 条

[21] Residue-specific bioincorporation of non-natural, biologically active amino acids into proteins as possible drug carders: Structure and stability of the per-thiaproline mutant of annexin V
Budisa, N.
Minks, C.
Medrano, F. J.
Lutz, J.
Proceedings of the National Academy of Sciences of the United States of America, 95 (02):
[22] Forced evolution of Escherichia coli cells with the ability to effectively utilize non-natural amino acids L-tert-leucine, L-norleucine and γ-methyl-L-leucine
Wang, Xing-Guo
Zhang, Pingping
Lynch, Susan
Engel, Paul C.
BIOCATALYSIS AND BIOTRANSFORMATION, 2010, 28 (5-6) : 293 - 303
[23] Residue-specific bioincorporation of non-natural, biologically active amino acids into proteins as possible drug carriers:: Structure and stability of the per-thiaproline mutant of annexin V
Budisa, N
Minks, C
Medrano, FJ
Lutz, J
Huber, R
Moroder, L
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (02) : 455 - 459
[24] A NOVEL-APPROACH TO THE SYNTHESIS OF OPTICALLY PURE NON-PROTEIN ALPHA-AMINO-ACIDS IN BOTH L-CONFIGURATION AND D-CONFIGURATION FROM L-SERINE
SASAKI, NA
HASHIMOTO, C
POTIER, P
TETRAHEDRON LETTERS, 1987, 28 (48) : 6069 - 6072
[25] A label-free strategy for immobilization of GPCRs using site-specific encoded non-natural amino acids to develop a selectively chromatographic approach for pursuing potential ligands binding to 5-hydroxytryptamine 1A receptor
Zhao, Xue
Xiang, Mingjuan
Zhang, Zilong
Li, Shiyan
Li, Ting
Qu, Lejing
Qiao, Sai
Li, Qian
Quan, Jia
Zhao, Xinfeng
JOURNAL OF CHROMATOGRAPHY A, 2024, 1718

← 1 2 3 →