Linchpins empower promiscuous electrophiles to enable site-selective modification of histidine and aspartic acid in proteins
Dattatraya Gautam Rawale, Kalyani Thakur, Pranav Sreekumar, T. K. Sajeev, A. Ramesh, Srinivasa Rao Adusumalli, Ram Kumar Mishra, Vishal Rai
Abstract
The conservation of chemoselectivity becomes invalid for multiple electrophilic warheads during protein bioconjugation. Consequently, it leads to unpredictable heterogeneous labeling of proteins. Here, we report that a linchpin can create a unique chemical space to enable site-selectivity for histidine and aspartic acid modifications overcoming the pre-requisite of chemoselectivity.
Topics & Concepts
ElectrophileHistidineAspartic acidChemistryReactivity (psychology)LysineBiochemistryCombinatorial chemistryComputational biologyAmino acidBiologyMedicinePathologyCatalysisAlternative medicineChemical Synthesis and AnalysisPeptidase Inhibition and AnalysisBiochemical and Structural Characterization