Studying the interaction between three synthesized heterocyclic sulfonamide compounds with hemoglobin by spectroscopy and molecular modeling techniques

The interaction between synthesized heterocyclic benzene sulfonamide compounds, N-(7-benzyl-56-biphenyl-2m-tolyl-7H-pyrrolo[23-d]pyrimidine–4–yl)-benzene sulfonamide (HBS₁), N-(7-benzyl-56-biphenyl-2-m-tolyl-7H-pyrrolo[23-d] pyrimidine-4-yl)-4-methyl- benzene sulfonamide (HBS₂), and N-(7-benzyl-56-biphenyl-2-m-tolyl-7H-pyrrolo[23-d]pyrimidine-4-yl)-4-chloro-benzene sulfonamide (HBS₃) with Hb was studied by fluorescence quenching, zeta potentional, circular dichroism, and molecular modeling techniques. The fluorescence spectroscopy experiments were performed in order to study the conformational changes, possibly due to a discrete reorganization of Trp residues during binding between HBS derivatives and Hb. The variation of the K_SV value suggested that hydrophobic and electrostatic interactions were the predominant intermolecular forces stabilizing the complex. The K_SV1 ans K_SV2 values of HBS derivatives with Hb are .6 × 10¹³ and 3 × 10¹³ M^?1 for Hb–HBS₁, 1 × 10¹³ and 4 × 10¹³ M^?1 for Hb–HBS₂, .9 × 10¹³, and 6 × 10¹³ M^?1 for Hb–HBS₃, respectively. The molecular distances between Hb and HBS derivatives in binary and ternary systems were estimated according to Förster’s theory of dipole–dipole non-radiation energy transfer. The quantitative analysis data of circular dichroism spectra demonstrated that the binding of the three HBS derivatives to Hb induced conformational changes in Hb. Changes in the zeta potential of the Hb–HBS derivatives complexes demonstrated a hydrophobic adsorption of the anionic ligand onto the surface of Hb as well as both electrostatic and hydrophobic adsorption in the case of the complex. The modeling data thus confirmed the experimental results. This study is expected to provide important insight into the interaction of Hb with three HBS derivatives to use in various toxicological and therapeutic processes.     

中药药效物质的研究方法

中药药效物质的研究是中药现代化研究的核心,科学阐明中药临床治疗的物质基础,是中药药效学研究的最终目标。现阶段中药药效物质基础研究方法主要有化学分离分析、生物色谱法和虚拟筛选等方法。本文对现有中药药效物质基础的几种研究方法进行了分类,并对其特点进行了介绍。     

Mechanisms of constraints: the contributions of selection and genetic variance to the maintenance of cotyledon number in wild radish

The evolutionary mechanisms underlying the maintenance of invariant traits are poorly understood, partly because the lack of variance makes these mechanisms difficult to study. Although the number of cotyledons that plant species produce is highly canalized, populations of plants frequently contain individuals with abnormal cotyledon numbers. In a garden study with 1857 wild radish plants from 75 paternal half-sibling families, 89 (almost 5%) had cotyledon numbers less or greater than two. We found evidence for direct selection on cotyledon number, but no evidence for additive genetic variation for cotyledon number. In spite of the very large sample size, our power to detect variation and selection was hampered by the small number of individuals (10) producing more than two cotyledons. Thus, our results provide support for both a lack of genetic variation and selection as reasons for the current lack of variation in wild radish cotyledon number.