Identification of a Receptor-Binding Region in Parathyroid Hormone*

Comparative Study of Chicken and Human Parathyroid Hormone‐(1–34)‐Peptides in Solution with SDS

“…It was reported that receptor-binding capacity involves the segment Arg25-Phe34 forming a major site and the segment AsnlO-Lys27 forming a minor site (Nussbaum et al, 1980;Rosenblatt et al, 1980). The deletion of residues 29-34 resulted in the decrease of binding affinity (Segre et al, 1979).…”

“…Phospholipid vesicles and mixed solvent systems such as trifluoroethanol and water have been employed to induce and stabilize secondary structures such as a-helix (Cohen et al, 1991;Nussbaum et al, 1980). Among several vesicles, the developments of an a-helix on hPTH fragments to l-palmitoyl-2-oleoylglycerophosphoserine (PamOleGroPSer) vesicles and dodecylphosphocholine micelle were reported (Epand et al, 1985a, b ;Neugebauer et al, 1992;Strickland et al, 1993).…”

International Union of Basic and Clinical Pharmacology. XCIII. The Parathyroid Hormone Receptors—Family B G Protein–Coupled Receptors

“…Further structure-activity relationship studies revealed that the PTH(15-34) sequence comprised the hormone's principal receptor-binding domain, because the PTH(15-34) peptide was the smallest fragment that retained at least some capacity to inhibit the binding of [ 125 I]PTH(1-34) radioligand to the receptor, albeit this binding was quite weak, with a K i value of ;1 Â 10 26 M, compared with that of PTH(1-34), which exhibits a K i value of around 1 Â 10 29 M Rosenblatt et al, 1980). Amino-terminal PTH fragments, such as PTH(1-14), could be inferred from the antagonist studies to contain the principal determinants of receptor signaling, but initially such peptides were found to be inert.…”

Solution Structure of Parathyroid Hormone Related Protein (Residues 1–34) Containing an Ala Substituted for an Ile in Position 15 (PTHrP[Ala15]-(1–34))

“…In particular, the substitution of Ser 3 by Glu 3 reduces both activity and binding by 3 log. However, simple deletion of the N-terminal six residues barely affects receptor binding while essentially abolishing activity in PTH (9) and PTHrP (10). Consequently, the presence of the N-terminal helical segment is unnecessary for maintaining strong receptor binding but modifications of side chains within it can act to sterically hinder binding.…”