The renaissance of peptides as prospective therapeutics has fostered the development of novel strategies for their synthesis and modification. In this context, besides the development of new chemical peptide ligation approaches, especially the use of enzymes as a versatile tool has gained increased attention. Nowadays, due to their inherent properties such as excellent regio- and chemoselectivity, enzymes represent invaluable instruments in both academic and industrial laboratories. This mini-review focuses on natural- and engineered peptide ligases that can form a new peptide (amide) bond between the -terminal carboxy and -terminal amino group of a peptide and/or protein. The pro's and cons of several enzyme classes such as Sortases, Asparaginyl Endoproteases, Trypsin related enzymes and as a central focus subtilisin-derived variants are summarized. Most recent developments with regards to ligation and cyclization are highlighted.
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http://dx.doi.org/10.3389/fchem.2019.00829 | DOI Listing |
Chemistry
January 2025
Xi'an Jiaotong University, School of Chemistry, No.28, West Xianning Road, 710049, Xi'an, CHINA.
Due to the diverse chemical and physical properties of functional groups, mild and controllable ligation methods are often required to construct complex drugs and functional materials. To make diverse sets of products with tunable physicochemical properties, it is also useful to employ complimentary ligation methods that adopt the same starting materials. Here, we disclose the efficient and modular synthesis of amides or thioamides through the chemical ligation of acyl silanes with amines, simply by turning a light on or off.
View Article and Find Full Text PDFOrg Lett
January 2025
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, China.
Here, we report on methods for late-stage peptide diversification through palladium-catalyzed site-selective C(sp)-H amination of tryptophan residues at the C4 position, utilizing tryptophan-amine cross-links. Our strategy enables practical access to C-N bonds, facilitating the construction of cyclopeptides via late-stage cyclodimerization of structurally complex peptides, which poses significant challenges for organic synthesis. The synthetic utility of this protocol is demonstrated through the synthesis of 30- to 38-membered macrocyclic peptides.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Department of Cardiology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510800, China.
Irbesartan improves ventricular remodeling (VR) following myocardial infarction (MI). This study investigates whether irbesartan attenuates VR by reducing aldosterone production in the heart and its underlying mechanisms. MI was induced in male Sprague-Dawley rats through coronary artery ligation.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
January 2025
Nankai University, SKLEOC, 300071, Tianjin, CHINA.
Amino groups are abundant in both natural and synthetic molecules, offering highly accessible sites for modifying native biorelevant molecules. Despite significant progress with more reactive thiol groups, methods for connecting two amino groups with reversible linkers for bioconjugation applications remain elusive. Herein, we report the use of oxidative decarboxylative condensation of glyoxylic acid to crosslink two alkyl amines via a compact formamidine linkage, applicable in both intra- and intermolecular contexts.
View Article and Find Full Text PDFBMC Complement Med Ther
January 2025
Institute of Basic Medical Sciences of Xiyuan Hospital, Beijing Key Laboratory of Chinese Materia Pharmacology, China Academy of Chinese Medical Sciences, National Clinical Research Center of Traditional Chinese Medicine for Cardiovascular Diseases, Beijing, China.
Objectives: This study intended to explore whether the protective effect safflower yellow injection (SYI) on myocardial ischemia-reperfusion (I/R) injury in rats mediated of the NLRP3 inflammasome signaling.
Methods: The I/R model was prepared by ligating the left anterior descending coronary artery for 45 min and then releasing the blood flow for 150 min. 96 male Wistar rats were randomly divided into sham group, I/R group, Hebeishuang group (HBS), SYI high-dose group (I/R + SYI-H), SYI medium-dose group (I/R + SYI-M) and SYI low-dose group (I/R + SYI-L).
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