Torino Domenica, Mollica Adriano, Pinnen Francesco, Feliciani Federica, Spisani Susanna, Lucente Gino
Dipartimento di Chimica e Tecnologie del Farmaco and Istituto di Chimica Biomolecolare, CNR Sezione di Roma, "Sapienza", Università di Roma, P.le A.Moro, 00185 Roma, Italy.
Bioorg Med Chem. 2009 Jan 1;17(1):251-9. doi: 10.1016/j.bmc.2008.11.010. Epub 2008 Nov 12.
cis-(2S,4S) 4-amino-proline (cAmp) and trans-(2S,4R) 4-amino-proline (tAmp) residues, bearing N-For or N-Boc substituents at the two amino groups, have been incorporated into the potent chemotactic agent fMLF-OMe in place of the N-terminal native (S)-methionine to give the analogues 17a-19a and 17b-19b. The new ligands have been examined for their activity (chemotaxis, superoxide anion production and lysozyme release) on human neutrophils as agonists and antagonists. Compounds 19a and 19b, bearing two N-For groups at the proline scaffold, are active and selective chemoattractants. The ligand 18b, containing N-For at the 4-amino group of the N-Boc-tAmp residue, exhibits significant chemotactic antagonism. The influence of the different substitution at the N-terminal position of the new analogues is discussed.
顺式-(2S,4S) 4-氨基脯氨酸（cAmp）和反式-(2S,4R) 4-氨基脯氨酸（tAmp）残基在两个氨基上带有N-甲酰基或N-叔丁氧羰基取代基，已被引入强效趋化剂fMLF-OMe中，取代了N端天然的（S）-甲硫氨酸，得到类似物17a - 19a和17b - 19b。已对这些新配体作为激动剂和拮抗剂对人中性粒细胞的活性（趋化性、超氧阴离子产生和溶菌酶释放）进行了研究。在脯氨酸骨架上带有两个N-甲酰基的化合物19a和19b是有活性的选择性趋化剂。在N-叔丁氧羰基-tAmp残基的4-氨基处含有N-甲酰基的配体18b表现出显著的趋化拮抗作用。讨论了新类似物N端位置不同取代的影响。
