Introducing Chemoselective Peptide Conjugation via N-Alkylation of Pyridyl-alanine: Solution and Solid Phase Applications

IF 4.9 1区化学 Q1 CHEMISTRY, ORGANIC Organic Letters Pub Date : 2024-09-13 DOI:10.1021/acs.orglett.4c03168

Soumit Dutta, Arnab Chowdhury, Anupam Bandyopadhyay

引用次数: 0

Abstract

A novel chemoselective peptide conjugation via late-stage N-alkylation of pyridyl-alanine (PAL) in the solution and solid phase, namely, NAP, is demonstrated. The method constructs functionally diverse and highly stable N-alkylated conjugates with various peptides. Notably, conjugations in the solid phase offered a more economical process. The method can provide the opportunity for dual labeling along with a cysteine handle in a peptide chain. Finally, we showcased that the antiproliferative activities of the p53 peptide (MDM2 inhibitor) could be 2-fold enhanced via NAP conjugation with the RGD peptide (selective integrin binder).

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通过吡啶基丙氨酸的 N-烷基化引入化学选择性多肽共轭：溶液和固相应用

通过在溶液和固相中对吡啶基丙氨酸（PAL）进行后期 N-烷基化（即 NAP），展示了一种新型化学选择性肽共轭方法。该方法能与各种肽构建出功能多样且高度稳定的 N-烷基化共轭物。值得注意的是，固相共轭过程更为经济。该方法还能为肽链中的半胱氨酸柄提供双重标记的机会。最后，我们展示了通过 NAP 与 RGD 肽（选择性整合素粘合剂）共轭，p53 肽（MDM2 抑制剂）的抗增殖活性可提高 2 倍。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Organic Letters 化学-有机化学

CiteScore

9.30

自引率

11.50%

发文量

1607

审稿时长

1.5 months

期刊介绍： Organic Letters invites original reports of fundamental research in all branches of the theory and practice of organic, physical organic, organometallic,medicinal, and bioorganic chemistry. Organic Letters provides rapid disclosure of the key elements of significant studies that are of interest to a large portion of the organic community. In selecting manuscripts for publication, the Editors place emphasis on the originality, quality and wide interest of the work. Authors should provide enough background information to place the new disclosure in context and to justify the rapid publication format. Back-to-back Letters will be considered. Full details should be reserved for an Article, which should appear in due course.