Therapeutic insulin, in its native and biosynthetic forms as well as several currently available insulin analogues, continues to be the protein of most interest to researchers. From the time of its discovery to the development of modern insulin analogues, this important therapeutic protein has passed through several stages and product generations. Beside the well-known link between diabetes and...

A number of nicotinamide adenine dinucleotide analogues have been prepared in which the purine, pyridine, and ribose moieties have been modified (2-12). These analogues have proven to be valuable in studies dealing with the site of binding of the pyridine coenzyme to dehydrogenases, in elucidating the mechanism of dehydrogenases and the configuration of the pyridme coenzymes, and as indicators ...

Although incorporation of nonnatural amino acids provides a powerful means of controlling protein structure and function, experimental investigations of amino acid analogues for utilization by the protein biosynthetic machinery can be costly and time-consuming. In this paper, we describe a computational protocol (HierDock) for predicting the relative energies of binding of phenylalanine analogu...

Recently described biphenyl analogues of the antituberculosis drug PA-824 displayed improved potencies against M. tuberculosis but were poorly soluble. Heterobiaryl analogues of these, in which the first phenyl ring was replaced with various 5-membered ring heterocycles, were prepared with the aim of identifying potent new candidates with improved aqueous solubility. The compounds were construc...

We report the solid-phase synthesis and some pharmacological properties of twenty oxytocin (OT) analogues. Basic modifications at position 7 (introduction of alpha-aminoisobutyric acid [Aib], L- or D-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid [L/D-Tic], L-alpha-t-butylglycine [Gly(Bu(t))] and pipecolic acid [Pip]) were combined with D-Tyr(Et)(2), L/D-(pEt)Phe(2), D-Tic(2), and Mpa(1) modi...

Fourteen tryptophan analogues have been characterized w ith regard to th e ir grow th inh ib ito ry effects on Catharanthus roseus cell cultures, their inh ib ito ry effect on an th ran ila te synthetase, their incorporation into protein and their substrate affin ity to try p to p h an decarboxylase. The toxicity of 12 o f the analogues was directly correlated w ith th e ir inh ib ito ry effect...

Insulin analogues have been engineered to enhance desired molecular properties without altering immunogenicity. The majority of insulin pharmacology studies are conducted in healthy volunteers and patients with type 1 diabetes. At present, there are more patients with type 2 than type 1 diabetes receiving insulin treatment. As the responsibility for initiating insulin therapy in these patients ...

Hyperbolic beta integrals are analogues of Euler’s beta integral in which the role of Euler’s gamma function is taken over by Ruijsenaars’ hyperbolic gamma function. They may be viewed as (q, q̃ )-bibasic analogues of the beta integral in which the two bases q and q̃ are interrelated by modular inversion, and they entail q-analogues of the beta integral for |q| = 1. The integrals under considerat...

In a recent paper, we presented a new definition of influences in product spaces of continuous distributions, and showed that analogues of the most fundamental results on discrete influences, such as the KKL theorem, hold for the new definition in Gaussian space. In this paper we prove Gaussian analogues of two of the central applications of influences: Talagrand’s lower bound on the correlatio...

The high-yielding synthesis of enantiomerically pure epicatechin gallate analogues where the A and/or B-ring hydroxylation is reduced or altered has been achieved by optimising routes to the catechin stereochemistry. The B-ring analogues were synthesised by using an electrophilic ring closure onto an enantiomerically enriched epoxide as a key step. The A and B-ring hydroxyl-deleted analogues we...