NOVEL CARBORANYL AMINO-ACIDS AND PEPTIDES - REAGENTS FOR ANTIBODY MODIFICATION AND SUBSEQUENT NEUTRON-CAPTURE STUDIES

被引:64
作者
VARADARAJAN, A [1 ]
HAWTHORNE, MF [1 ]
机构
[1] UNIV CALIF LOS ANGELES,DEPT CHEM & BIOCHEM,LOS ANGELES,CA 90024
关键词
D O I
10.1021/bc00010a008
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
A new alpha-amino acid derivative incorporating the 1,2-dicarba-closo-dodecarborane(12) cage, namely 5-(2-methyl-1,2-dicarba-closo-dodecarborane(12)-l-yl)-2-aminopentanoic acid (2), was synthesized by the alkylation of the benzophenone Schiff's base of glycine methyl ester with 3-(2-methyl-1,2-dicarba-closo-dodecaborane (12)-1-yl)propyl iodide (8). This amino acid was employed in the synthesis of peptide derivatives such as 19-21 using solid-phase Merrifield methods. Dipeptide 19 was converted to a water-soluble ionic derivative by the pyrrolidine-mediated carborane cage degradation reaction followed by cation exchange to afford sodium salt 22. Dansylation of 22 with dansyl chloride yielded fluorescence-labeled dipeptide 23. Undecapeptide 21 was dansylated while still anchored to the Merrifield resin. Following its cleavage from the resin with hydrogen fluoride, product 25 was acetylated to block the free amino group on the lysine residue and then converted to water-soluble derivative 27. Trial conjugations of dipeptide 23 and undecapeptide 27 to T84.66, an anti-CEA antibody, were carried out by means of carboxyl activation with N-hydroxysulfosuccinimide and NN-diisopropylcarbodiimide. Studies of the chemical syntheses of these and other peptide derivatives and the conjugation of 23 and 27 to the antibody are described.
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页码:242 / 253
页数:12
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