TY - JOUR
T1 - Native-compound-Coupled Affinity Matrix (NCAM) in target identification and validation of bioactive compounds
T2 - Application, mechanism and outlooks
AU - Ma, Lu
AU - Li, Menglong
AU - Gou, Shanshan
AU - Wang, Wei
AU - Liu, Kangdong
AU - Zhang, Yueteng
N1 - Publisher Copyright:
© 2023 Elsevier Inc.
PY - 2023/11
Y1 - 2023/11
N2 - In drug discovery and development, the direct target identification of bioactive small molecules plays a significant role for understanding the mechanism of action, predicting the side effects, and rationally designing more potent compounds. However, due to the complicated regulatory processes in a cell together with thousands of biomacromolecules, target identification is always the major obstacle. New methods and technologies are continuously invented to tackle this problem. Nevertheless, the mainly used tools possess several disadvantages. High synthetic skills are typically required to laboriously synthesize a probe for protein enrichment. To detect the ligand–protein interaction by analyzing proteins’ responses to proteolytic or thermal treatment, costly and precise instruments are always necessary. Therefore, convenient and practical techniques are urgently needed. Over the past decades, a strategy using native compounds without the requirement of chemical modification, also termed Native-compound-Coupled Affinity Matrix (NCAM), is developing continuously. Two practical tactics based on “label-free” compounds have been invented and used, that is Photo-cross-linked Small-molecule Affinity Matrix (PSAM) and Native-compound-Coupled CNBr-activated Beads (NCCB). Presently, we will elucidate the characteristics, coupling mechanism, advantages and disadvantages, and future prospect of NCAM in specific target identification and validation.
AB - In drug discovery and development, the direct target identification of bioactive small molecules plays a significant role for understanding the mechanism of action, predicting the side effects, and rationally designing more potent compounds. However, due to the complicated regulatory processes in a cell together with thousands of biomacromolecules, target identification is always the major obstacle. New methods and technologies are continuously invented to tackle this problem. Nevertheless, the mainly used tools possess several disadvantages. High synthetic skills are typically required to laboriously synthesize a probe for protein enrichment. To detect the ligand–protein interaction by analyzing proteins’ responses to proteolytic or thermal treatment, costly and precise instruments are always necessary. Therefore, convenient and practical techniques are urgently needed. Over the past decades, a strategy using native compounds without the requirement of chemical modification, also termed Native-compound-Coupled Affinity Matrix (NCAM), is developing continuously. Two practical tactics based on “label-free” compounds have been invented and used, that is Photo-cross-linked Small-molecule Affinity Matrix (PSAM) and Native-compound-Coupled CNBr-activated Beads (NCCB). Presently, we will elucidate the characteristics, coupling mechanism, advantages and disadvantages, and future prospect of NCAM in specific target identification and validation.
KW - Chemical proteomics
KW - Mechanism of action
KW - Native compounds
KW - Pharmacology
KW - Target validation
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UR - http://www.scopus.com/inward/citedby.url?scp=85170284317&partnerID=8YFLogxK
U2 - 10.1016/j.bioorg.2023.106828
DO - 10.1016/j.bioorg.2023.106828
M3 - Article
C2 - 37690368
AN - SCOPUS:85170284317
SN - 0045-2068
VL - 140
JO - Bioorganic Chemistry
JF - Bioorganic Chemistry
M1 - 106828
ER -