A “dock, lock, and latch” Structural Model for a Staphylococcal Adhesin Binding to Fibrinogen

AbstractGram-positive pathogens such as staphylococci contain multiple cell wall-anchored proteins that serve as an interface between the microbe and its environment. Some of these proteins act as adhesins and mediate bacterial attachment to host tissues. SdrG is a cell wall-anchored adhesin from Staphylococcus epidermidis that binds to the Bβ chain of human fibrinogen (Fg) and is necessary and sufficient for bacterial attachment to Fg-coated biomaterials. Here, we present the crystal structures of the ligand binding region of SdrG as an apoprotein and in complex with a synthetic peptide analogous to its binding site in Fg. Analysis of the crystal structures, along with mutational studies of both the protein and of the peptide, reveals that SdrG binds to its ligand with a dynamic “dock, lock, and latch” mechanism. We propose that this mechanism represents a general mode of ligand binding for structurally related cell wall-anchored proteins of gram-positive bacteria

Identifying the components of the solid–electrolyte interphase in Li-ion batteries

The importance of the solid–electrolyte interphase (SEI) for reversible operation of Li-ion batteries has been well established, but the understanding of its chemistry remains incomplete. The current consensus on the identity of the major organic SEI component is that it consists of lithium ethylene di-carbonate (LEDC), which is thought to have high Li-ion conductivity, but low electronic conductivity (to protect the Li/C electrode). Here, we report on the synthesis and structural and spectroscopic characterizations of authentic LEDC and lithium ethylene mono-carbonate (LEMC). Direct comparisons of the SEI grown on graphite anodes suggest that LEMC, instead of LEDC, is likely to be the major SEI component. Single-crystal X-ray diffraction studies on LEMC and lithium methyl carbonate (LMC) reveal unusual layered structures and Li+ coordination environments. LEMC has Li+ conductivities of >1 × 10−6 S cm−1, while LEDC is almost an ionic insulator. The complex interconversions and equilibria of LMC, LEMC and LEDC in dimethyl sulfoxide solutions are also investigated

Synthesis and pharmacological properties of oxytocin analogs having penicillamine

Six analogs of oxytocin having penicillamine (L or D) at position 1,​p-​hydroxyphenylglycine (Hpg, L or D) at position-​2 and​/or threonine (L or D) at position-​4 have been synthesized by the solid-​phase method and tested for oxytocic, antioxytocic and antidiuretic activities. All the six analogs antagonize the action of oxytocin on rat uterus in the presence of Mg2+ in vitro. One of the analogs, [L-​Pen1,​L-​Hpg2]​-​oxytocin, is a dose-​dependent potent inhibitor of oxytocic activity. They also exhibit low antidiuretic activity

Synthesis and biological activity of some new leucine-enkephalin analogues

The opioid pentapeptide leucine-enkephalinamide and eleven of its analogues have been synthesised by the solid phase technique employing mostly 9-fluoroenylmethyloxycarbonyl amino acid active esters in the presence of 1-hydroxybenzotriazole. Both the conventional chloromethylated copolystyrene-2 divinylbenzene resin as well as p-alkoxybenzyl alcohol resin were employed and it was observed that yields were uniformly better with the latter resin. The analogues were made by affecting single or multiple replacements of amino acids involving positions 1,2 and 5. Some of the analogues were found to be more potent than morphine in the guinea pig ileum assay. © 1985 Indian Academy of Sciences

New analogues of leucine-methionine-enkephalin

Nine analogues of the opioid pentapeptides leucine-/ methionine-enkephalinamide, involving replacement of amino acid at position 5 or amino acids at positions 2 and 5, have been synthesized by the solid phase method using mainly 9-fluorenylmethyloxycarbonyl amino acid trichlorophenyl esters in the presence of 1-hydroxybenzotriazole, the solid support being the Merrifield resin. All the analogues were effective in inhibiting the electri cally stimulated contractions of the guinea pig ileum (in vitro) and one of them, tyrosyl-Dnorvalyl-glycyl-phenylalanyl-methioninamide was found to be about 82 times more active than morphine. They also exhibited analgesic activity as well as antidiarrhoeal activity in mice (in vivo). © 1988 Indian Academy of Sciences

Synthesis and pharmacological properties of oxytocin analogues having penicillamine

Six analogs of oxytocin having penicillamine (L or D) at position 1,​p-​hydroxyphenylglycine (Hpg, L or D) at position-​2 and​/or threonine (L or D) at position-​4 have been synthesized by the solid-​phase method and tested for oxytocic, antioxytocic and antidiuretic activities. All the six analogs antagonize the action of oxytocin on rat uterus in the presence of Mg2+ in vitro. One of the analogs, [L-​Pen1,​L-​Hpg2]​-​oxytocin, is a dose-​dependent potent inhibitor of oxytocic activity. They also exhibit low antidiuretic activity

Catalytic transfer hydrogenation of aromatic nitro compounds employing formic acid in presence of palladium black

Arom. nitro compds. like nitrophenols and nitroamines were reduced by catalytic transfer hydrogenation using formic acid in the presence of Pd black. The reaction rate is greatly enhanced by the addn. of a small quantity of sodium formate

Synthesis and biological activities of new analogs of dermorphin substituted at position-​2

Seven analogs of demorphin with different D-​amino acids at position 2 have been obtained by the solid-​phase method using mainly 9-​fluorenylmethoxycarbonyl amino acid active esters in the presence of 1-​hydroxybenzotriazole, the solid support being the Merrifield resin. Their pharmacol. effects have been studied in vitro by the guinea pig ileum (GPI) assay and in vivo by the hot plate method. The antidiarrheal properties of these peptides have also studied in mice (in vivo)​. [D-​Nva2]​- and [D-​Eth2]​-​dermorphin (Nva = norvaline; Eth = ethionine) approach morphine in the GPI assay and hot plate test resp. Though, in general, replacement of D-​Ala2 by other D-​amino acids leads to lower GPI and analgesic activities, there is an enhancement of antidiarrheal potency in the case of four analogs, the most active one being [D-​Phe2]​-​dermorphin, which is 2.7 times more potent than morphine

Synthesis and biological activity of analogues of leucine-/methionine-enkephalin

Seven analogues of opioid pentapeptides leucine-/methionine-enkephalinamides have been synthesised by the solid phase technique employing mainly 9-fluorenylmethyloxycarbonyl amino acid active esters in presence of 1-hydroxybenzotriazole and the conventional chloromethylated copolystyrene-2% divinylbenzene (Merrifield) resin as the solid support. The analogues were obtained by replacing the amino acids at positions 2 and 5. Some of the analogues were found, to be highly potent in the guinea pig ileum assay