Molar extinction coefficients of some carbohydrates in aqueous solutions

Molar extinction coefficients of some carbohydrates viz. l-arabinose (C₅H₁₀O₅), d-glucose (C₆H₁₂O₆), d-mannose (C₆H₁₂O₆), d-galactose (C₆H₁₂O₆), d(-) fructose (C₆H₁₂O₆) and maltose (C₁₂H₂₄O₁₂) in aqueous solutions have been determined at 81, 356, 511, 662, 1173 and 1332 keV by gamma ray transmission method in a narrow beam good geometry set-up. These coefficients have been found to depend upon the photon energy following a 4-parameter polynomial. These extinction coefficients for different sugars having the same molecular formula have same values varying within experimental uncertainty. Within concentration ranges studied, Beer-Lambert law is obeyed very well.     

Synthesis and biological activity of cyclic peptide inhibitors of ribonucleotide reductase

[formula: see text] A series of lactam-bridged peptide inhibitors (2-6) of mammalian ribonucleotide reductase (mRR) has been designed and synthesized on the basis of the heptapeptide N-AcFTLDADF (1), corresponding to the C-terminus of the R2 subunit of mRR. Inhibition studies revealed a direct relation between ring size and activity, with peptide 5 being 2.5 times more potent than peptide 1.     

Rational polynomial representation of ribonucleotide reductase activity

Background  

Recent data suggest that ribonucleotide reductase (RNR) exists not only as a heterodimer R1₂R2₂ of R1₂ and R2₂ homodimers, but also as tetramers R1₄R2₄ and hexamers R1₆R2₆. Recent data also suggest that ATP binds the R1 subunit at a previously undescribed hexamerization site, in addition to its binding to previously described dimerization and tetramerization sites. Thus, the current view is that R1 has four NDP substrate binding possibilities, four dimerization site binding possibilities (dATP, ATP, dGTP, or dTTP), two tetramerization site binding possibilities (dATP or ATP), and one hexamerization site binding possibility (ATP), in addition to possibilities of unbound site states. This large number of internal R1 states implies an even larger number of quaternary states. A mathematical model of RNR activity which explicitly represents the states of R1 currently exists, but it is complicated in several ways: (1) it includes up to six-fold nested sums; (2) it uses different mathematical structures under different substrate-modulator conditions; and (3) it requires root solutions of high order polynomials to determine R1 proportions in mono-, di-, tetra- and hexamer states and thus RNR activity as a function of modulator and total R1 concentrations.     

Dichlorocarbene Addition to

In contrast to the terminal phosphinidene complex PhPW(CO)(5) (2), which adds to [5]metacyclophane (1) in a 1,4-fashion, dichlorocarbene preferentially adds in a 1,2-fashion to the formal "anti-Bredt" type double bond of the aromatic ring of 1 to afford the norcaradiene 11b, which immediately rearranges to the bridged cycloheptatriene 12b and further by a [1,5] sigmatropic chlorine migration to the isomeric 13b as the first observable product. More slowly, the latter isomerizes via a dissociative mechanism to give 15b. A computational study supports the notion that the [1,5] chlorine migration in the rearrangement 12b --> 13b, for which an activation barrier of 70.2 kJ mol(-)(1) was calculated, is essentially concerted with minor charge separation. In contrast, the analogous [1,5] chlorine migration in the flat model compound 7,7-dichlorocycloheptatriene (12a) displays features of a dissociative pathway.     

Molecular docking of cathepsin L inhibitors in the binding site of papain

The papain/CLIK-148 coordinate system was employed as a model to study the interactions of a nonpeptide thiocarbazate inhibitor of cathepsin L ( 1). This small molecule inhibitor, a thiol ester containing a diacyl hydrazine functionality and one stereogenic center, was most active as the S-enantiomer, with an IC 50 of 56 nM; the R-enantiomer ( 2) displayed only weak activity (33 microM). Correspondingly, molecular docking studies with Extra Precision Glide revealed a correlation between score and biological activity for the two thiocarbazate enantiomers when a structural water was preserved. The molecular interactions between 1 and papain were very similar to the interactions observed for CLIK-148 ( 3a and 3b) with papain, especially with regard to the hydrogen-bonding and lipophilic interactions of the ligands with conserved residues in the catalytic binding site. Subsequent docking of virtual compounds in the binding site led to the identification of a more potent inhibitor ( 5), with an IC 50 of 7.0 nM. These docking studies revealed that favorable energy scores and correspondingly favorable biological activities could be realized when the virtual compound design included occupation of the S2, S3, and S1' subsites by hydrophobic and aromatic functionalities of the ligand, and at least three hydrogen bonding contacts between the ligand and the conserved binding site residues of the protein.