Polymeres porteurs de greffons peptidiques: Polymérisation et copolymérisation de monomères styréniques parasubstitués par des oligopeptides

Polymers and copolymers with peptide pendant chains have been prepared by polymerization and copolymerization of styrene with para styryl peptide monomers terminated by a carboxylic acid or primary amine group.

Polymerizations of I and II have been initiated by AIBN, in tetrahydrofuran or N,N-dimethylformamide. For polymers with functional ends on side-chains protected by urethane functions (amino group) or ester function (acid group), polymer regeneration has been carried out by acidolysis (urethane) and basic hydrolysis (ester). The influences of monomer structure on polymerization yield and the water solubility after neutralisation, have been considered. Copolymerizations of styrene with I and II have been studied. Random copolymers, with solubility in various solvents depending on their composition, have been obtained. Reactivity ratios have been determined.     

Structure activity relationship by NMR and by computer: a comparative study

There has recently been considerable interest in using NMR spectroscopy to identify ligand binding sites of macromolecules. In particular, a modular approach has been put forward by Fesik et al. (Shuker, S. B.; Hajduk, P. J.; Meadows, R. P.; Fesik, S. W. Science 1996, 274, 1531-1534) in which small ligands that bind to a particular target are identified in a first round of screening and subsequently linked together to form ligands of higher affinity. Similar strategies have also been proposed for in silico drug design, where the binding sites of small chemical groups are identified, and complete ligands are subsequently assembled from different groups that have favorable interactions with the macromolecular target. In this paper, we compare experimental and computational results on a selected target (FKBP12). The binding sites of three small ligands ((2S)1-acetylprolinemethylester, 1-formylpiperidine, 1-piperidinecarboxamide) in FKBP12 were identified independently by NMR and by computational methods. The subsequent comparison of the experimental and computational data showed that the computational method identified and ranked favorably ligand positions that satisfy the experimental NOE constraints.     

Carbohydrate-protein interactions at interfaces: synthesis of thiolactosyl glycolipids and design of a working model for surface plasmon resonance

Thiolactosyl lipids designed for carbohydrate-protein binding studies have been synthesised. One representative was selected for binding studies with a plant lectin RCA120, the agglutinin from Ricinus communis. The interactions were measured quantitatively in real time using a BIAcore surface plasmon resonance instrument. Removal of much of the galactose from the thiolactosyl lipid in situ with beta-galactosidase showed that the lectin binding was highly specific. A dissociation constant KD = 8.77 x 10(-8) M was measured for 1-[2-[2-(2-[beta-D-galactopyranosyl-(1-->4)-1-thio-beta-D -glucopyranosyl]ethoxy)ethoxy]ethoxy]octadecane 30 which is four orders of magnitude greater than that determined for binding to lactose in solution. A concentration of lactose of > 80 mM was required to block the lectin binding to thiolactosyl lipid in a neomembrane.     

Highly stereoselective Friedel-Crafts type cyclization. Facile access to enantiopure 1,4-dihydro-4-phenyl isoquinolinones

The present report describes a stereoselective synthesis of 1,4-dihydro-4-phenyl isoquinolinones 5 based on a stereoselective Friedel-Crafts type cyclization. Cyclization precursors 1 were prepared in two steps, from the readily available (S)-mandelic acid, in 60-80% overall yield. The stereoselective electrophilic cyclization was accomplished in 20-86% yield and with 20-97% ee. In the course of this work, the presence of the amide carbonyl was found to be particularly important to guarantee a stereospecific process during the electrophilic aromatic substitution.     

Total synthesis of zincophorin methyl ester

[reaction: see text]. A convergent total synthesis of the methyl ester of zincophorin, an ionophore antibiotic, has been realized relying on a diastereoselective titanium-mediated aldol coupling between the C1-C12 and C13-C25 subunits. The latter fragment was prepared by using a Carroll-Claisen rearrangement.     

Study of polymer treatment with tetrafluoromethane plasma: Reactivity of fluorinated species on model surfaces

Polyolefins and their model molecules, some n-alcanes, have been modified by a tetrafluoromethane microwave plasma. The chosen molecules are high-density polyethylene (HDPE) and hexatriacontane (HTC), low-density polyethylene (LDPE) and paraffin, and polycaprolactone (PCL) and octadecyl octadecanoate (ODO). It has been found, except for paraffin, that the model surfaces have the same behavior as the corresponding polymers. Plasma modification is described as the sum of two mechanisms: degradation and fluorination. These reactions seem to be competitive and parallel. Degradation and fluorination rates are dependent on treatment time and are practically independent on substrate position. A domain of fluorination exists near the edge of plasma, whatever the substrate in or outside plasma. © 1993 John Wiley & Sons, Inc.     

Chemoselective and stereoselective synthesis of gem-difluoro-β-aminoesters or gem-difluoro-β-lactams from ethylbromodifluoroacetate and imines during Reformatsky reaction

The chemoselective and stereoselective synthesis of gem-difluoro-β-aminoesters or gem-difluoro-β-lactams was investigated from ethylbromodifluoroacetate and imines during Reformatsky reaction. Influence of various reaction parameters, such as nature of the amine part, nature of the chiral auxiliary, was evaluated. High levels of stereoselectivity (up to 98%) were obtained for gem-difluoro-β-aminoesters and gem-difluoro-β-lactams using either (R)-phenylglycinol or (R)-methoxyphenylglycinol.     

Synthesis of New,Unnatural Macrocyclic Trichothecenes: 3-isoverrucarin A ((1″-O)(3→4)abeo-verrucarin A), verrucinol,and verrucene. 46th Communication on verrucarins and roridins

A new unnatural macrocyclic trichothecene, an analogue of verrucarine A ( 1 ), which was named 3-Isoverrucarin A ((1″-O)(3→4)abeo-verrucarin A; 3 ) was synthesized starting from anguidine ( 5 ). The two key reactions were the removal of the 4β-acetoxy group of anguidine ( 5 ) by a Barton deoxygenation and the final macrolactonization. During the cyclization procedure, two unexpected new macrocyclic by-products, which were named verrucinol ( 19 ) and verrucene ( 20 ), were formed. They represent novel types of macrocyclic trichothecenes, the macrolidic moiety of verrucene ( 20 ) consisting only of the (Z,E)-muconic-acid residue. The formation of the analogous macrolide 26 of verrucene ( 20 ) was not possible, probably because the ring strain is too strong.     

Acid-base properties of xanthosine 5'-monophosphate (XMP) and of some related nucleobase derivatives in aqueous solution: micro acidity constant evaluations of the (N1)H versus the (N3)H deprotonation ambiguity

The first acidity constant of fully protonated xanthosine 5'-monophosphate, that is, of H3(XMP)+, was estimated by means of a micro acidity constant scheme and the following three deprotonations of the H2(XMP)+/- (pKa=0.97), H(XMP)- (5.30), and XMP2- (6.45) species were determined by potentiometric pH titrations; further deprotonation of (XMP-H)3- is possible only with pKa>12. The most important results are that the xanthine residue is deprotonated before the P(O)2(OH)- group loses its final proton; that is, twofold negatively charged XMP carries one negative charge in the pyrimidine ring and one at the phosphate group. Micro acidity constant evaluations reveal that this latter mentioned species occurs with a formation degree of 88 %, whereas its tautomer with a neutral xanthine moiety and a PO3(2-) group is formed only to 12 %; this distinguishes XMP from its related nucleoside 5'-monophosphates, like guanosine 5'-monophosphate. At the physiological pH of about 7.5 mainly (XMP-H)3- exists. The question, which of the purine sites, (N1)H or (N3)H, is deprotonated in this species cannot be answered unequivocally, though it appears that the (N3)H site is more acidic. By application of several methylated xanthine species intrinsic micro acidity constants are calculated and it is shown that, for example, for 7-methylxanthine the N1-deprotonated tautomer occurs with a formation degree of about 5 %; a small but significant amount that, as is discussed, may possibly be enhanced by metal ion coordination to N7, which is known to occur preferably to this site.