Chemical Synthesis of the 20 kDa Heme Protein Nitrophorin 4 by α-Ketoacid-Hydroxylamine (KAHA) Ligation

Angewandte Chemie
Chunmao HeJeffrey W Bode

Abstract

The chemical synthesis of the 184-residue ferric heme-binding protein nitrophorin 4 was accomplished by sequential couplings of five unprotected peptide segments using α-ketoacid-hydroxylamine (KAHA) ligation reactions. The fully assembled protein was folded to its native structure and coordinated to the ferric heme b cofactor. The synthetic holoprotein, despite four homoserine residues at the ligation sites, showed identical properties to the wild-type protein in nitric oxide binding and nitrite dismutase reactivity. This work establishes the KAHA ligation as a valuable and viable approach for the chemical synthesis of proteins up to 20 kDa and demonstrates that it is well-suited for the preparation of hydrophobic protein targets.

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Citations

Mar 5, 2016·Journal of the American Chemical Society·Ji-Shen ZhengLei Liu
May 27, 2016·Nature Protocols·Thibault J HarmandJeffrey W Bode
Aug 2, 2016·Journal of the American Chemical Society·Chi Lung LeeXuechen Li
Sep 28, 2016·Chemical Reviews·Renata Marcia de FigueiredoJean-Marc Campagne
Nov 3, 2016·Journal of the American Chemical Society·Kenneth E Schwieter, Jeffrey N Johnston
Feb 8, 2020·Angewandte Chemie·Claudia E MurarJeffrey W Bode
Dec 20, 2018·Organic & Biomolecular Chemistry·Chong ZuoJi-Shen Zheng
Aug 30, 2017·Accounts of Chemical Research·Jeffrey W Bode

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