onto cracked ice. The title compound precipitated as a white solid. Filtration, washing with water, and air-drying gave the product: 0.93 g (66.5%); mp 145 °C. Recrystallization from ethyl acetate provided the analytical sample: mp 147-148 °C; NMR (Me2SO-de) 5.98 (s, 2, CH2), 7.95 (s, 1, H-2), 9.75 (hr s, 1, NH); mass spectrum (70 eV), m/e (relative intensity) 188 (M+, 23), 142

Most peptides have not proved useful as neuroactive drugs because they are blocked by the blood-brain barrier and do not reach their receptors within the brain.Intraperitoneally administered L-serinyl JD-glucosde aalgues of [Metslenkephaln (glycopeptides) have been shown to be transported across the blood-brain barrier to bind with targeted p and &oplod receptors in the mouse brain. The opioid nature of the bing has been demonstrated with intracerebroventricularly a ered naloxone. Paradoxically, glucosylation decreases the ipophlt of the peptides while promoting transport across the phc endothe layer. It is suggested that glucose transporter GLUT-1 is responsible for the transport of the peptide message. Profound and long-lasting anesla has been observed in mice (tail-ck and hot-plate assays) with two of the glycopeptide a ues when administered intraperitoneally.

We have previously reported the chemistry and antinociceptive properties of a series of glycosylated enkephalin analogs (glycopeptides) exhibiting approximately equal affinity and efficacy at ␦ opioid receptors (DORs) and opioid receptors (MORs).

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The synthesis of 18 N-alpha-FMOC-amino acid glycosides for solid-phase glycopeptide assembly is reported. The glycosides were synthesized either from the corresponding O'Donnell Schiff bases or from N-alpha-FMOC-amino protected serine or threonine and the appropriate glycosyl bromide using Hanessian's modification of the Koenigs-Knorr reaction. Reaction rates of D-glycosyl bromides (e.g., acetobromoglucose) with the L- and D-forms of serine and threonine are distinctly different and can be rationalized in terms of the steric interactions within the two types of diastereomeric transition states for the D/L and D/D reactant pairs. The N-alpha-FMOC-protected glycosides [monosaccharides Xyl, Glc, Gal, Man, GlcNAc, and GalNAc; disaccharides Gal-beta(1-4)-Glc (lactose), Glc-beta(1-4)-Glc (cellobiose), and Gal-alpha(1-6)-Glc (melibiose)] were incorporated into 22 enkephalin glycopeptide analogues. These peptide opiates bearing the pharmacophore H-Tyr-c[DCys-Gly-Phe-DCys]- were designed to probe the significance of the glycoside moiety and the carbohydrate-peptide linkage region in blood-brain barrier (BBB) transport, opiate receptor binding, and analgesia.

Endogenous peptides (e.g. enkephalins) control many aspects of brain function, cognition, and perception. The use of these neuroactive peptides in diverse studies has led to an increased understanding of brain function. Unfortunately, the use of brain-derived peptides as pharmaceutical agents to alter brain chemistry in vivo has lagged because peptides do not readily penetrate the blood-brain barrier. Attachment of simple sugars to enkephalins increases their penetration of the blood-brain barrier and allows the resulting glycopeptide analogues to function effectively as drugs. The delta-selective glycosylated Leu-enkephalin amide 2, H(2)N-Tyr-D-Thr-Gly-Phe-Leu-Ser(beta-D-Glc)-CONH(2), produces analgesic effects similar to morphine, even when administered peripherally, yet possesses reduced dependence liability as indicated by naloxone-precipitated withdrawal studies. Similar glycopeptide-based pharmaceuticals hold forth the promise of pain relief with improved side-effect profiles over currently available opioid analgesics.

Rhamnolipids are amphiphilic glycolipids biosynthesized by bacteria that, due to their low toxicity and biodegradability, are potential replacements for synthetic surfactants. The previously limited access to pure materials at the gram scale has hindered extensive characterization of rhamnolipid structure-performance behavior. Here, we present an efficient and versatile synthetic methodology from which four diastereomers of the most common monorhamnolipid, α-rhamnopyranosyl-β-hydroxydecanoyl-β-hydroxydecanoate, are prepared and subsequently characterized. Exploration of their behavior at the air-water interface is reported and analyzed in terms of the absolute configuration of the lipid tail carbinols at pH 4.0 and 8.0. All diastereomers exhibit a minimum surface tension of about 28 mN/m without a significant difference between the protonated (nonionic) or deprotonated (anionic) states. At pH 4.0 (nonionic), all diastereomers have a critical micelle concentration (CMC) in the micromolar range. At pH 8.0 (anionic), CMC values for the (R,R), (S,S), and (S,R) diastereomers are approximately an order of magnitude higher than in their nonionic states, whereas the (R,S) diastereomer exhibits a CMC about five times larger.

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