Late-Stage Solubilization of Poorly Soluble Peptides Using Hydrazide Chemistry

Kohei Sato; Shoko Tanaka; Junzhen Wang; Kenya Ishikawa; Shugo Tsuda; Tetsuo Narumi; Taku Yoshiya; Nobuyuki Mase

doi:10.1021/acs.orglett.1c00074

Late-Stage Solubilization of Poorly Soluble Peptides Using Hydrazide Chemistry

Org Lett. 2021 Mar 5;23(5):1653-1658. doi: 10.1021/acs.orglett.1c00074. Epub 2021 Feb 11.

Authors

Kohei Sato^{1

2

3}, Shoko Tanaka³, Junzhen Wang¹, Kenya Ishikawa¹, Shugo Tsuda⁴, Tetsuo Narumi^{1

2

3

5}, Taku Yoshiya⁴, Nobuyuki Mase^{1

2

3

5}

Affiliations

¹ Department of Applied Chemistry and Biochemical Engineering, Faculty of Engineering, Shizuoka University, 3-5-1 Johoku, Hamamatsu, Shizuoka 432-8561, Japan.
² Course of Applied Chemistry and Biochemical Engineering, Department of Engineering, Graduate School of Integrated Science and Technology, Shizuoka University, 3-5-1 Johoku, Hamamatsu, Shizuoka 432-8561, Japan.
³ Graduate School of Science and Technology, Shizuoka University, 3-5-1 Johoku, Hamamatsu, Shizuoka 432-8561, Japan.
⁴ Peptide Institute, Inc., 7-2-9 Saito-Asagi, Ibaraki, Osaka 567-0085, Japan.
⁵ Research Institute of Green Science and Technology, Shizuoka University, 3-5-1 Johoku, Hamamatsu, Shizuoka 432-8561, Japan.

PMID: 33570416
DOI: 10.1021/acs.orglett.1c00074

Abstract

A novel late-stage solubilization of peptides using hydrazides is described. A solubilizing tag was attached through a selective N-alkylation at a hydrazide moiety with the aid of a 2-picoline-borane complex in 50% acetic acid-hexafluoro-2-propanol. The tag, which tolerates ligation and desulfurization conditions, can be detached by a Cu-mediated selective oxidative hydrolysis of the N-alkyl hydrazide. This new method was validated through the synthesis of HIV-1 protease.

Publication types

Research Support, Non-U.S. Gov't