Search

Research points out that the growth inhibitory activity of the brain specific metallothionein-3 is due to local structural differences and global dynamics in the beta-domain of the protein as revealed by solution NMR studies. Data indicate that the growth inhibitory activity is confined to a CPCP tetrapeptide at the N-terminus.

A study was conducted to analyze the bisphosphatase domain determined from the rat liver 6-phosphofructor-2-kinase/fructose-2,6-bisphosphatase. 1H-13C HMQC nuclear magnetic resonance spectroscopy was carried out on the histidine C2' and H2' nuclei. the plasmids were determined from expression plasmids for the bifunctional and bisphosphatase domain constructs. The wild-type and mutant bisphosphatase domains were then labeled with 13C at the ring C2' of the histidine residues.

A study was conducted to test the hypothesis that single-pass fractional hydrolysis of benzoyl-phenylalanyl-glycyl-proline (BPGP) in the lung may reflect the cis-trans ratio of angiotensin-converting enzyme (ACE) molecules exposed to the flowing blood. Nuclear magnetic resonance spectroscopy a cis-trans ratio of 44:56. Single-pass hydrolysis resulted in hydrolysis of only 59% of BPGP while hydrolysis by ACE led to the hydrolysis of 60% of the substrate, suggesting that the trans isomer is preferentially hydrolyzed by ACE.

Examination of the solution structure of Callinectes sapidus metallothionein-1 by multinuclear NMR correlation experiments reveals the existence of two distinct domains in the metallothionein-1. A cluster of three metal ions in these domain exhibits a tetrahedral coordination with the S(gamma) of the nine Cys residues existing in each domain. Bridging of two metal ions involves six Cys residues, and twelve Cys residues function as terminal ligands. Interdomain short distance constraints are absent in this protein, and various type I beta turns are present as regular secondary structure.

Two-dimensional NMR analysis and transferred nuclear Overhauser effect of peptidyl prolyl cis-trans isomerase (PPIase) reveal that the cyclophilin (CyP)-bound substrate cis-like conformation with A-P peptide bond is out of planarity by not more than 40 degrees. CyP is the cytosol receptor of the immunosuppressant cyclosporin A. The 9,10 cyclosporin A peptide conformation changes are possibly unrelated to PPIase catalysis.

Yeast metallothioneins (MTS) are small, cystein-rich proteins binding to heavy metals such as Cu and Zn and nonessential metals such as Cd and Hg. A structural analysis of MTS reveals a duplication in the backbone proton resonance signals from residue K41 located on the C-terminus. By determining the coupling constant, hydrogen exchange and NOE data, the presence of numerous type I beta-turns and the absence of other characteristic secondary structural element can be detected.

The secondary structures in aqueous solution of two biologically active Arg-Gly-Asp (RGD) oligopeptides were investigated by two-dimensional proton nuclear magnetic resonance spectroscopy. It was found that the sequence Tyr=Gly-Arg-Gly-Asp-Ser-Pro assumes a tye II beta turn at both pH 4 and 7. Thispeptide binds to selected cell surface receptors. In contrast, the oligopeptidewhich has a conservative subsitution of Glu for Asp in the RGD sequence assumesa type I or III beta turn at both pH 4 and 7. The results suggest that oligopeptides assume structures in solutions that have biological significance.

The structural features of the active immunosuppressive drug, cyclosporin A (CsA), and a nonactive analog of CsA werestudied using a cyclophilin (CyP) deuteration strategy and nuclear magnetic resonance spectroscopy. Fully deuterated CyP was produced by expressing the human CyP gene in Escherichia coli grown on deuterated algal hydrolysate in D2O. The drug analog, MeAla6-CsA, was shown to bind tightly to CyP but does notexhibit immunosuppressive activity.

In efforts to optimize a manufacturing process for an internal development compound, a clean, efficient approach to guanidine synthesis using chloroformamidine hydrochloride was identified. To investigate the general utility of this methodology towards electron-deficient , a set of favorable conditions were developed from a series of screens, and the scope of the reaction was probed. The successful application of this chemistry to a variety of pyridines, anilines, and heterocyclic compounds highlights its use as an improved, alternative guanylation method for this often challenging set of . [ABSTRACT FROM AUTHOR]