Gupta Manish K, Mishra Pradeep, Prathipati Philip, Saxena Anil K
Medicinal Chemistry Division, Central Drug Research Institute, Lucknow, India.
Bioorg Med Chem. 2002 Dec;10(12):3713-6. doi: 10.1016/s0968-0896(02)00421-2.
Peptide deformylase catalyzes the removal of N-formyl group from the N-formylmethionine of ribosome synthesized polypeptide in eubacteria. Quantitative structure-activity relationship (QSAR) studies have been carried out in a series of beta-sulfonyl and beta-sulfinyl hydroxamic acid derivatives for their PDF enzyme inhibitory and antibacterial activities against Escherichia coli DC2 and Moraxella catarrhalis RA21 which demonstrate that the PDF inhibitory activity in cell free and whole cell system increases with increase in molar refractivity and hydrophobicity. The comparison of the QSARs between the cell free and whole cell system indicate that the active binding sites in PDF isolated from E. coli and in M. catarrhalis RA21 are similar and the whole cell antibacterial activity is mainly due to the inhibition of PDF. Apart from this the QSARs on some matrixmetelloproteins (COL-1, COL-3, MAT and HME) and natural endopeptidase (NEP) indicate the possibilities of introducing selectivity in these hydroxamic acid derivatives for their PDF inhibitory activity.
肽脱甲酰基酶催化真细菌中核糖体合成多肽的N-甲酰甲硫氨酸的N-甲酰基去除。已经对一系列β-磺酰基和β-亚磺酰基异羟肟酸衍生物进行了定量构效关系（QSAR）研究，以考察它们对大肠杆菌DC2和卡他莫拉菌RA21的肽脱甲酰基酶（PDF）抑制活性和抗菌活性，结果表明在无细胞和全细胞体系中，PDF抑制活性随摩尔折射率和疏水性的增加而增强。无细胞体系和全细胞体系之间的QSAR比较表明，从大肠杆菌分离的PDF和卡他莫拉菌RA21中的活性结合位点相似，全细胞抗菌活性主要归因于对PDF的抑制作用。除此之外，对一些基质金属蛋白酶（COL-1、COL-3、MAT和HME）和天然内肽酶（NEP）的QSAR研究表明，这些异羟肟酸衍生物有可能因其PDF抑制活性而具有选择性。
