ABSTRACT
Conventional methods of peptide chemistry have been used to synthesize the C-terminal nonapeptide from human immunoglobulin E, which is a potential cytophilic binding site of the IgE molecule responsible for its primary recognition and binding to specific target cell receptors.
Subject(s)
Immunoglobulin E/chemical synthesis , Immunoglobulin Fragments/chemical synthesis , Peptide Fragments/chemical synthesis , Amino Acid Sequence , HumansABSTRACT
Peptides corresponding to sequences of the Fc-portion of immunoglobulin G (IgG) surrounding and containing the tuftsin molecule were synthesized. The compounds were assayed for their ability to compete with [3H-Arg4]tuftsin in binding to mouse peritoneal macrophages and to stimulate the cell's capacity to phagocytize. Despite the sensitivity that tuftsin has demonstrated to various chemical modifications and structural alterations which usually cause reduction or total loss of biological activity, IgG-related analogs possess potent tuftsin-like activity. The activity is not caused by enzymatic breakdown and release of tuftsin. The fact that the elongated tuftsin analogs can specifically be attached to and activate macrophages may indicate a possible connection between Fc and tuftsin's receptors.
Subject(s)
Immunoglobulin Fragments/chemical synthesis , Immunoglobulin G , Peptide Fragments/chemical synthesis , Receptors, Immunologic , Tuftsin/chemical synthesis , Amino Acid Sequence , Animals , Biological Assay , Indicators and Reagents , Kinetics , Macrophages/drug effects , Macrophages/metabolism , Mice , Peptide Fragments/pharmacology , Phagocytosis/drug effects , Receptors, Cell Surface/metabolism , Structure-Activity Relationship , Tuftsin/metabolism , Tuftsin/pharmacologyABSTRACT
The cyclization, under alkaline conditions, of N-benzyloxycarbonyl-L-threonine and of N-benzyloxycarbonyl-L-serine to produce 5-methyl-2-oxo-oxazolidine-4-carboxylic acid (O = C Thr1 and 2-oxo-oxazolidine-4-carboxylic acid (O = C Ser), respectively, was investigated and found to be efficient and racemization-free. Similar was the cyclization which accompanied the basic hydrolysis of N-benzyl-oxycarbonyl-L-threonyl-L-phenylalanine methyl ester and of N-benzyloxy-carbonyl-L-seryl-DL-valine ethyl ester, and which resulted in the formation of L - O = C Thr-L-Phe and L - O = C Ser-DL-Val, respectively. The reaction was applied to the synthesis of [O = C Thr1] tuftsin, an active analog of the phagocytosis stimulating peptide tuftsin. A new synthetic route to tuftsin is also described.