Biomedical subjects
Publications and source records attributed to B M Rode.
Experiments with reduced-charge montmorillonites with gradually collapsed interlayer space prove that peptide formation processes occur mainly at the edges of the clay mineral. Activation of peptides and amino acids and the intermediate formation of cyclic anhydrides are found to be the two dominant processes determining the formation of higher peptides on the mineral surface.
Several studies have proven the ability of montmorillonite to catalyse amino acid condensation under assumed prebiotic conditions, simulating wetting-drying cycles. In this work, the oligomerization of short peptides gly2, gly3, gly4 and ala2 on Ca- and Cu-montmorillonite in drying-wetting cycles at 80 degrees C was studied. The catalytic effect of montmorillonite was found to be much higher than in the case of glycine oligomerization. From gly2 after 3 weeks, 10% oligomers (up to gly6, with gly3 as main products) are formed. Gly3 and gly4 give higher oligomers even after 1 cycle. Ala2 produces both ala3 and ala4, whereas ala does not produce any oligomers under these conditions. Heteroologomerization was observed: ala-gly-gly is formed from ala and gly2. Much higher yields are obtained using Ca-montmorillonite, because copper (II) oxidizes organic molecules. The influence of the reaction mechanism on the preferential oligomerization of oligopeptides is discussed.
Evaporation cycles applied to dilute solutions of amino acids, Cu(II) and NaCl lead to peptides within 1-3 days. This simulation of possible coastal or laguna processes in a primitive earth environment gives further indications towards the relevance of the salt-induced peptide formation reaction in chemical evolution. The experiments were successfully applied to glycine, alanine, aspartic and glutamic acid. Besides isolated amino acids, also their mixtures with glycine as reaction partner were studied, leading to peptides for all of the aforementioned substances, as well as for valine and proline, which do not dimerize alone. Sequence preferences and some conservation of optical purity were observed.
The applicability of the salt-induced peptide formation in aqueous solution--the simplest model so far for peptide synthesis under primitive earth conditions--is demonstrated for valine as another amino acid, and the formation of mixed peptides in systems containing glycine, alanine and valine is investigated. The dominant dipeptides formed are Gly-Gly, Gly-Ala and Gly-Val, at longer reaction times sequence inversion produces Ala-Gly and, considerably slower, Val-Gly. Ala-Ala is also produced and the relative amounts of the diastereomers prove the high conservation of optical purity of the original amino acids over a considerable time. The results lead to some further conclusions about the reaction mechanism and the possible dominance of peptide sequences in primordial dipeptides.
1. The interaction of zinc and cadmium ion with human serum albumin (HSA) is evaluated and compared by potentiometric titration method and computer simulation of complex equilibria. 2. Zinc binds to histidine and free amino groups, cadmium in addition to basic functional groups of the protein. 3. Whereas zinc binds stronger in 1:1 complexes, chelate binding favours cadmium ions. 4. Within biological pH-conditions, high amounts Zn(II) and even more of Cd(II) will be bound to HSA.
A mouse monoclonal anti-2,4,6-trinitrophenyl IgE (clone Lb4) was screened with a random set of over 2000 compounds, and several ligands were found to bind with affinities comparable to that of the immunizing hapten (KD in the microM range). An automated docking algorithm was used for the prediction of complex structures formed by 2,4-dinitrophenyl (DNP) and non-DNP ligands in the fragment variable region of IgE(Lb4). All ligands were found to dock in an L-shaped cavity of 15 x 16 x 10 A, surrounded by complementary-determining regions L1, L3, H2 and H3. The ligands were found to occupy the same binding site in different orientations. For rigid ligands the most stable orientation could be predicted with high probability, based on the calculated energy of binding and the occurrence frequencies of identical complexes obtained by repeated simulations. The localization of a flexible ligand (cycrimine-R) was more ambiguous, but it still docked in the same site. The results support a model for heteroligating antibody (Ab) binding sites, where different ligands utilize the total set of available contacts in different combinations. It is suggested that although pseudoenergies calculated by the docking algorithm do not correlate with experimentally measured binding energies, the screening-and-docking procedure can be useful for the mapping of Ab and other receptor binding sites ligating small molecules.
The interaction of mono- and divalent metal ions with the nucleic acid base pairs A:T and G:C has been studied using ab initio self-consistent field Hartree-Fock computations with minimal basis sets. Energy-optimized structures of the two base pairs with a final base-base distance of L = 10.35 A have been determined and were further used in calculations on ternary complexes Mn+ - A:B together with previously computed coordination geometries of the cations at adenine (Ade), thymine (Thy), and guanine (Gua). Besides the binding energy of the various metal ions to the base pairs, changes in the stability of the H bonds between Ade and Thy or Gua and Cyt have been determined. Polarization effects of the metal ion on the ligand turned out to increase the binding between complementary bases. Regardless of the metal species, cation binding to Gua N(3) and Thy O(2) leads to a special increase in H-bond stability, whereas binding to Ade N(3) changes the H-bond stability least. Situated in between are the stabilizing effects caused by Gua and Ade N(7) coordination. A remarkable relation between the stability of the H bond and the distance from metal binding site to H bonds was found. This relationship has been rationalized in terms of partial charges of the atoms participating in H bonding, which can reveal the trend in the electrostatic part of total H bond energy. It can be shown that a short distance between coordination site and acceptor hydrogen increases the H-bond strength substantially, while a long distance shows minor effects as supposed. On the other hand, the opposite effect is observed for the influence of the distance between binding site and donor atom. A comparison of our findings with a new model of transition metal ion facilitated rewinding of denatured DNA proposed by S. Miller, D. VanDerveer, and L. Marzilli is given [(1985) J. Am. Chem. Soc. 107, 1048-1055].
Optimal nonlinear transformations provided by alternating conditional expectations (ACE) method are used to study the relationship between electronic structure and antimalarial activity of mefloquine and its substituted derivatives. The electronic structure of these molecules is featured by atomic net charges evaluated on the basis of CNDO/2 molecular orbital calculations. A comparison to multiple linear regression (MLR) and partial least squares (PLS) method is also included. The results show that ACE can be a useful and well-suited technique for establishing QSAR and predicting the pharmacological activity of compounds.