Conjugates of catecholamines. VII. Synthesis and β‐adrenergic activity of peptide catecholamine conjugates†

Abstract
A series of novel catecholamine derivatives has been prepared in which one of the N-methyl substituents of isoproterenol has been extended by a spacer consisting of a chain of four methylenes which terminates with an amide linkage to a peptide, the point of attachment being via the aromatic amino group of p-aminophenylalanine. In one of the derivatives, two catecholamines are attached to the same peptide in this manner. The peptides, which range in size from three to eight amino acid residues and contain phenylalanine, glycine, and L-.alpha.-amino-.delta.-hydroxyvaleric acid, were synthesized via stepwise and fragment condensation techniques. The .beta.-adrenergic agonist activities of the derivatives were evaluated in vitro by measuring the intracellular accumulation of cyclic AMP in S49 mouse lymphoma cells.

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