Arginine-lysine-aspartic acid-valine-tyrosine polypeptide(s) - induce differentiation of T lymphocytes but not that of B lymphocytes having complement receptor and are used to increase immunity

摘要

Polypeptide derivs. containing the active group of formula (I) have the ability to cause by induction the differentiation T lymphocytes but not that of B lymphocytes having the complement receptor (CR+). The novel polypeptides of formula (II) and their salts are partic. claimed. In the formula R,R1 are terminal gps. joined to the polypeptide which do not influence its biological activity; R is H, 1-7C alkyl, 5-12C aryl, 6-20C alkaryl, 6-20C aralkyl, 1-7C alkanoyl, 1-7C alkenyl, 1-7C alkynyl, Gln, Glu, Gly, Glu-Gln, Gly-Gln, Gly-Glu or Gly-Glu-Gln; R1 is hydroxy-NH2, -NHR, -N(R)2, -OR7, X, Val, Gln, Leu, Tyr, Val-Glyn; Val-Leu, Val-Tyr, Gln-Leu, Gln-Tyr, Gln-Val, Leu-Tyr, Leu-Leu, Tyr-Leu, Val-Gln-Leu, Val-Gln-Leu-Tyr or Val-Glyn-Leu-Tyr-Leu; R7 is 1-7C alkyl, 1-7C alkynyl, 6-20C aryl, 6-20C aralkyl or 6-20C alkaryl and X is halo. Polypeptide intermediate of formula (III) is also novel, (where R1,R2,R3,R4, R5 are protecting groups; R1,R2,R3 and R4 are fixed on the reactive side-chain; R5 is fixed to the alpha-aminoacid and may be removed under conditions which do not remove R1,R2,R3 and R4; the resin is a physically stable, insoluble polymer joined by a covalent bond to the adjacent aminoacid. Typicall R1=tosyl, R2=epsilon-2-chlorobenzyloxycarbonyl; R3=benzyl; R4=0-2,6-dichloro benzyl and R5=amyloxycarbonyl. Typical resins used are cellulose, polymetharcrylate, sulphonated polystyrene and chloromethylated copolymer of styrene and divinylbenzene copolymer of styrene and divinylbenzene. (I) and (II) cause differentiation of bone marrow cells to give T cells, which give rise to the thymus lymphocytes, and are used in the immunitary system of animals and humans. They are used to terat Digeorge syndrome (congenital absence of thymus) and to stimulate immunity in chronic infections e.g. fungal infections due to mycoplasms, tuberculosis, leprosy, chronic and acute viral infections etc. The cpds. are also of interest in auto-immune illness where their are undesered antibodies e.g. generalised ery themateous lupus. They also influence neuromuscular transmission and may be used to treat spasticity.