PMID- 29888818 OWN - NLM STAT- MEDLINE DCOM- 20190603 LR - 20190603 IS - 1521-3765 (Electronic) IS - 0947-6539 (Linking) VI - 24 IP - 44 DP - 2018 Aug 6 TI - Exfoliated Nanosheets of a Cu(II) Coordination Polymer Modulate Enzyme Activity of alpha-Chymotrypsin. PG - 11297-11302 LID - 10.1002/chem.201802376 [doi] AB - A 2D coordination polymer derived from 5-azidoisophthalic acid (AIA) and Cu(NO(3) )(2) was designed with the aim of modulating the activity of a digestive enzyme alpha-chymotrypsin (ChT). The coordination polymer namely [Cu(0.5) (mu-AIA)(0.5) (H(2) O)]⋅2 H(2) O(alpha) (CP1) was successfully synthesized and fully characterized by single-crystal X-ray diffraction (SXRD). An exfoliated nanosheet (ENS) of CP1 was readily produced by overnight stirring of hand-ground CP1 crystals dispersed in DMSO. ENS(CP1) was demonstrated to be acting as an inhibitor of ChT; as much as approximately 97 % inhibition of ChT was achieved with 100 mum of ENS(CP1) using N-succinyl-l-phenylalanine-p-nitroanilide (SPNA) as substrate. Enzyme kinetics data revealed that the inhibition of ChT followed a competitive pathway. An enzyme assay under varying ionic strength and varying concentration of free histidine revealed that the active site His-57 participated in coordination with the Cu(II) metal center of ENS(CP1) thereby preventing the substrate (SPNA) from binding with the enzyme resulting in efficient inhibition. CI - (c) 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. FAU - Sarkar, Koushik AU - Sarkar K AD - Department of Organic Chemistry, Indian Association for the Cultivation of Science (IACS), 2A and 2B, Raja S. C. Mullick Road, Jadavpur, Kolkata, 700032, West Bengal, India. FAU - Dastidar, Parthasarathi AU - Dastidar P AUID- ORCID: 0000-0002-1011-2386 AD - Department of Organic Chemistry, Indian Association for the Cultivation of Science (IACS), 2A and 2B, Raja S. C. Mullick Road, Jadavpur, Kolkata, 700032, West Bengal, India. LA - eng PT - Journal Article DEP - 20180710 PL - Germany TA - Chemistry JT - Chemistry (Weinheim an der Bergstrasse, Germany) JID - 9513783 RN - 0 (Coordination Complexes) RN - 0 (Phthalic Acids) RN - 0 (Polymers) RN - 2440-62-2 (Suphepa) RN - 3600-77-9 (5-azidoisophthalic acid) RN - 47E5O17Y3R (Phenylalanine) RN - 4QD397987E (Histidine) RN - 789U1901C5 (Copper) RN - EC 3.4.21.1 (Chymotrypsin) RN - EC 3.4.21.1 (alpha-chymotrypsin) SB - IM MH - Animals MH - Binding Sites MH - Catalysis MH - Cell Survival/drug effects MH - Chymotrypsin/*antagonists & inhibitors/chemistry MH - Coordination Complexes/*chemical synthesis/chemistry/pharmacology MH - Copper/*chemistry MH - Histidine/chemistry MH - Kinetics MH - Mice MH - Models, Molecular MH - Nanostructures/*chemistry MH - Osmolar Concentration MH - Phenylalanine/analogs & derivatives/chemistry MH - Phthalic Acids/*chemistry MH - Polymers/*chemical synthesis/chemistry/pharmacology MH - Protein Conformation MH - RAW 264.7 Cells OTO - NOTNLM OT - biocompatibility OT - coordination polymer OT - enzymatic modulation OT - exfoliation OT - alpha-chymotrypsin EDAT- 2018/06/12 06:00 MHDA- 2019/06/04 06:00 CRDT- 2018/06/12 06:00 PHST- 2018/05/12 00:00 [received] PHST- 2018/06/06 00:00 [revised] PHST- 2018/06/12 06:00 [pubmed] PHST- 2019/06/04 06:00 [medline] PHST- 2018/06/12 06:00 [entrez] AID - 10.1002/chem.201802376 [doi] PST - ppublish SO - Chemistry. 2018 Aug 6;24(44):11297-11302. doi: 10.1002/chem.201802376. Epub 2018 Jul 10.