Study of Immunosuppressive Activity of a Synthetic Decapeptide Corresponding to an ACTH-Like Sequence of Human Immunoglobulin G1

E. V. Navolotskaya^1*, T. A. Zargarova¹, T. N. Lepikhova¹, V. I. Turobov¹, R. I. Nurieva¹, N. V. Malkova¹, V. M. Lipkin¹, and V. P. Zav'yalov²

¹Branch of Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Pushchino, Moscow Region, 142292 Russia; fax: (0967) 79-0527; E-mail: navolots@fibkh.serpukhov.su

²Institute of Engineering Immunology, Lyubuchany, Moscow Region, 142380 Russia; fax: (095) 546-1574

^* To whom correspondence should be addressed.

Received February 11, 1999

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The synthetic ACTH-like decapeptide H-Val-Lys-Lys-Pro-Gly- Ser-Ser-Val-Lys-Val-OH, corresponding to amino acid residues 11-20 of the variable part of the human IgG1 heavy chain (referred to as immunocortin) was found to have an immunosuppressive effect on cells in vitro: it inhibits blast transformation of mouse thymocytes and reduces spontaneous motility of mouse peritoneal macrophages as well as their bactericidal activity against the virulent bacterial strain Salmonella typhimurium 415. Tritium-labeled immunocortin binds with high affinity to ACTH receptors on thymocytes and macrophages (K_d 2.1 and 2.5 nM, respectively) and activates adenylate cyclase in these cells. Thus, the interaction of immunocortin with the target cell includes the following main steps: binding to the receptor, activation of adenylate cyclase, and elevation of the intracellular content of cAMP.

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KEY WORDS: adrenocorticotropic hormone (ACTH), immunoglobulin G (IgG), peptides, receptors, adenylate cyclase, thymocytes, peritoneal macrophages, immune system

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