The magnitude of a one-bond C-H coupling constant depends upon the chemical environment of the hydrogen atom and, especially, upon its stereochemical relationship to vicinal lone electron pairs. However, a lone electron pair is not essential for the observation of a stereoelectronic effect, since even cyclohexane exhibits different axial and equatorial C-H coupling constants. We propose the name "Perlin Effect" to describe such observations. An analysis of the extensive experimental data regarding the Perlin Effect reveals that, in cyclohexane and in six-membered rings having one or more heteroatoms of the first row attached to the carbon of interest, ' J~-~ is always larger for an equatorial hydrogen than for an axial hydrogen. The magnitude of the Perlin Effect is reduced when the carbon carrying the hydrogen of interest is attached to first row and second row atoms or heteroatoms, and it reverses when the carbon atom carries two heteroatoms from below the first row.The existence of the Perlin Effect in nuclear magnetic resonance spectra is reminiscent of an infrared effect known as the Bohlmann bands, whose origin has previously been explained by quantitative perturbational molecular orbital (PMO) theory in terms of the effects of lone electron pairs upon the lengths and strengths and, therefore, the chemical reactivities of vicinal C-H bonds. Since the magnitude of a one-bond C-H coupling constant is expected to vary inversely with bond length, the origins of the Perlin Effect and of the Bohlmann bands would seem to be the same, i.e., the longer (weaker) C-H bond has the smaller one-bond coupling constant. This expectation has now been confirmed: for 25 molecules, representing a total of 35 different kinds of C-H bonds, the bond lengths, stretching force constants, and charge distributions have been determined from fully optimized 6-3 1 G* molecular orbital calculations. In nine of ten cases for which experimental data exist for pairs of diastereomeric or diastereotopic hydrogens, the shorter C-H bond of the pair has the larger coupling constant; in the tenth case, the experimental difference is only 1-2 Hz. Moreover, a global analysis of the data in terms of the equationwhere J is an experimental coupling constant, q is a total atomic charge, and r is a C-H bond length, correlates 23 different types of C-H bonds linearly with a correlation coefficient of 0.9 15. The C parameter is the leading term of the correlation. Among the systems studied theoretically are eight molecules of the type CH3CHXY (Y = OH, SH; X = F, C1, OH, SH), which are representative of systems containing both endocyclic and exocyclic first row and second row anomeric effects. The exocyclic effect is found to be very similar for first row and second row substituents, but the endocyclic effect is larger for the first row substituent. Both findings agree with experimental data in solution. Finally, quantitative PMO analysis has been employed to analyse the origins of the different C-H bond lengths in the various molecules of the study. dans...

To investigate the molecular basis of antigenic mimicry by peptides, we studied a panel of closely related mAbs directed against the cell-wall polysaccharide of group A Streptococcus. These antibodies have restricted V-gene usage, indicating a shared mechanism of binding to a single epitope. Epitope mapping studies using synthetic fragments of the cell-wall polysaccharide supported this conclusion. All of the mAbs isolated crossreactive peptides from a panel of phagedisplayed libraries, and competition studies indicated that many of the peptides bind at or near the carbohydrate binding site. Surprisingly, the peptides isolated by each mAb fell into distinct consensus-sequence groups that discriminated between the mAbs, and in general, the peptides bound only to the mAbs used for their isolation. Similar results were obtained with polyclonal antibodies directed against synthetic oligosaccharide fragments of the streptococcal cell-wall polysaccharide. Thus, the peptides appear to be specific for their isolating antibodies and are not recognized by the same mechanism as their carbohydrate counterparts.Carbohydrates (CHOs) have proven to be valuable tools in demonstrating immunologic mimicry. Anti-idiotypic antibodies (Abs) directed against the V domains of anti-CHO Abs can, in some instances, elicit CHO-binding Ab responses when used themselves as immunogens (e.g., refs. 1-4). This has been attributed to chemical similarity (known as the ''internal image'') between an anti-idiotypic Ab and the corresponding CHO antigen (1). Likewise, crossreactive peptides have been identified for several anti-CHO mAbs (4-7). In one case, the peptide was shown to elicit Abs having the same idiotype as the cognate, anti-CHO mAb (5), and in another to elicit a CHObinding response (4).The work described here addresses the molecular basis of crossreactivity between CHO and protein antigens with Abs. Our goal was to determine if the crossreactive peptides recognized by anti-CHO Abs would bind by the same mechanism as the corresponding epitope on the CHO target; if so, the basis of crossreactivity would be structural mimicry. We assembled a panel of five closely related mAbs against the cell-wall polysaccharide (CWPS) of group A Streptococcus (GAS) and showed by oligosaccharide mapping studies that they indeed bind a similar, if not identical, epitope. Each of four anti-GAS CWPS mAbs and three polyclonal Abs (PCAbs) against synthetic oligosaccharide fragments of the GAS CWPS isolated peptides bearing unique, chemically distinct consensus sequences. Moreover, representative peptides from each consensus group were functionally specific, because they usually bound only to their isolating Ab. Thus, these Abs were more restricted in their peptide reactivity than in their CHO recognition. We conclude that the predominating basis of peptide recognition by anti-CHO Abs differs between Abs, with true CHO mimics being relatively rare. We propose that the antigenic mimicry observed for CHO-crossreactive peptides is determined mainly by the ...

Salacinol (4) is one of the active principles in the aqueous extracts of Salacia reticulata that are traditionally used in Sri Lanka and India for the treatment of diabetes. The syntheses of salacinol (4), the enantiomer of salacinol (5), and a diastereomer (7) are described. The synthetic strategy relies on the selective nucleophilic attack of 2,3,5-tri-O-benzyl-1,4-anhydro-4-thio-D- or L-arabinitol at C-1 of 2,4-O-benzylidene D- or L-erythritol-1,3-cyclic sulfate. The work serves to resolve the ambiguity about the exact structure of salacinol and establishes conclusively the structure of the natural product.

The antigenic recognition of Shigella flexneri O-polysaccharide, which consists of a repeating unit ABCD [-->2)-alpha-L-Rhap-(1-->2)-alpha-L-Rhap-(1-->3)-alpha-L-Rhap-(1-->3)-beta-D-GlcpNAc-(1-->], by the monoclonal antibody SYA/J6 (IgG3, kappa) has been investigated by crystallographic analysis of the Fab domain and its two complexes with two antigen segments (a pentasaccharide Rha A-Rha B-Rha C-GlcNAc D-Rha A' and a modified trisaccharide Rha B-Rha C-GlcNAc D in which Rha C* is missing a C2-OH group). These complex structures, the first for a Fab specific for a periodic linear heteropolysaccharide, reveal a binding site groove (between the V(H) and V(L) domains) that makes polar and nonpolar contacts with all the sugar residues of the pentasaccharide. Both main-chain and side-chain atoms of the Fab are used in ligand binding. The charged side chain of Glu H50 of CDR H2 forms crucial hydrogen bonds to GlcNAc of the oligosaccharides. The modified trisaccharide is more buried and fits more snugly than the pentasaccharide. It also makes as many contacts (approximately 75) with the Fab as the pentasaccharide, including the same number of hydrogen bonds (eight, with four being identical). It is further engaged in more hydrophobic interactions than the pentasaccharide. These three features favorable to trisaccharide binding are consistent with the observation of a tighter complex with the trisaccharide than the pentasaccharide. Thermodynamic data demonstrate that the native tri- to pentasaccharides have free energies of binding in the range of 6.8-7.4 kcal mol(-1), and all but one of the hydrogen bonds to individual hydroxyl groups provide no more than approximately 0.7 kcal mol(-1). They further indicate that hydrophobic interactions make significant contributions to binding and, as the native epitope becomes larger across the tri-, tetra-, pentasaccharide series, entropy contributions to the free energy become dominant.