Land T, Langel U, Löw M, Berthold M, Undén A, Bartfai T
Department of Biochemistry, Arrhenius Laboratories, Stockholm University, Sweden.
Int J Pept Protein Res. 1991 Sep;38(3):267-72. doi: 10.1111/j.1399-3011.1991.tb01438.x.
The neuropeptide galanin (1-29) binds with high affinity to hypothalamic receptors (KD approximately 0.9 nM) and regulates feeding behavior. The N-terminal fragments (1-16), (1-16)NH2 are high affinity (KD approximately 6 nM) full agonists in vivo and in vitro. L-Ala substitutions show that amino acid residues Gly1, Trp2, Asn5, Tyr9, and Gly12 are important for the high affinity binding of galanin (1-16). Shortening the fragment (1-16) to galanin (1-7) causes a gradual drop of affinity: galanin (1-15), (1-14), and (1-13) have submicromolar KD values and galanin (1-12) has KD approximately 3 microM. Cyclic analogs of galanin (1-12) of different ring size were synthesized by condensing Gly1 and Gly12 without or with spacer groups. These analogs, independent of ring size, had a lower affinity than the linear galanin (1-12). Derivatization of the N-terminus of galanin (1-29), (1-16), and (1-12) all resulted in a large drop of affinity for the receptors, suggesting again the importance of the free N-terminal Gly.
