1,8-Naphthyridin-2,7-(1,8H)-dione is an effective mimic of protonated cytosine in peptide nucleic acid triplex recognition systems.

A novel bicyclic mimic of protonated cytosine [1,8-naphthyridin-2,7-(1,8H)-dione, (K)] for Hoogsteen type triplex recognition of guanine has been designed for incorporation into peptide nucleic acids. Bis-PNA clamps with the K base incorporated in the Hoogsteen strand showed a significant stabilization of the triplexes at pH 7 as compared to similar triplexes with PNA oligomers containing either cytosine (6.7 degrees C per unit) or pseudoisocytosine (1.

Substituted 1,8-naphthyridin-2(1H)-ones are superior to thymine in the recognition of adenine in duplex as well as triplex structures.

The synthesis and evaluation of a series of novel nucleobases based on substituted 1,8-naphthyridin-2(1H)-ones are reported. The nucleobases were designed to meet the requirements for incorporation into peptide nucleic acids (PNAs) and were evaluated as part of PNA duplex and triplex nucleic acid recognition systems. Of the various nucleobases tested, only the 7-chloro-1,8-naphthyridin-2(1H)-one (7-Cl-bT) nucleobase led to consistently increased affinity in all recognition systems, duplex (Watson-Crick) as well as triplex (Hoogsteen).

Secondary structure of the third extracellular loop responsible for ligand selectivity of a mammalian gonadotropin-releasing hormone receptor.

The extracellular loop 3 (ECL3) of the mammalian gonadotropin-releasing hormone receptor (GnRH-R) contains an acidic amino acid (Glu(301) in the mouse GnRH-R) that confers agonist selectivity for Arg(8) in mammalian GnRH. It is proposed that a specific conformation of ECL3 is necessary to orientate the carboxyl side chain of the acidic residue for interaction with Arg(8) of GnRH, which is supported by decreased affinity for Arg(8) GnRH but not Gln(8) GnRH when an adjacent Pro is mutated to Ala. To probe the structural contribution of the loop domain to the proposed presentation of the carboxyl side chain, we synthesized a model peptide (CGPEMLNRVSEPGC) representing residues 293-302 of mouse ECL3, where Cys and Gly residues are added symmetrically at the N and C termini, respectively, allowing the introduction of a disulfide bridge to simulate the distances at which the ECL3 is tethered to the transmembrane domains 6 and 7 of the receptor.