Synthesis of New Peptidic Glycoclusters Derived from .BETA.-Alanine. Part 2: Optionally Modulated Distance between Side-Chain Branched Points

Abstract

It is worthwhile noting that multivalency is a powerful design approach to increase the binding strength of synthetic carbohydrate ligands with protein receptors.1-3) Some carbohydrate chemists have developed methods to make glycoclusters for that reason, [4][5][6][7][8] however, these clusters are symmetrical structures and there are few asymmetrical ones. Asymmetrical clusters are expected not only to enhance binding affinity but also may resolve steric conformation of protein receptors. Therefore, we have devised three types of new glycocluster (Fig. 1). In our previous paper, 9) we synthesized the glycocluster using diverse 'glycocluster units' that make it possible to modulate optionally the length of the side chain by insertion of w-amino acid as spacer between the main chain and the carbohydrate moiety (Fig. 1B). The glycocluster units are composed of b-alanine derivative as a clusterchain unit, sugar unit and w-amino acids as a spacer. They provide diversity using different w-amino acids between the cluster-chain unit and sugar unit. This method is advantageous for the synthesis of diverse glycoclusters to combine several diverse glycocluster units.It is also important to consider not only side chain length but also the distance between the side chain branched points to give diversity to the glycoclusters. The steric distribution of carbohydrate residues on glycoconjugates will affect their interaction with lectins. Therefore, two kinds of w-amino acids (b-alanine and 6-aminocapronic acid) as spacers of different length were attached to the cluster-chain unit, and diverse glycocluster units were synthesized. The glycoclusters were elongated by coupling these units (Fig. 1C).In this paper we report the synthesis of glycocluster 1 which makes it possible to modulate optionally the distance between the side chain branch points (Fig. 2). Furthermore, we undertook to build a glycodendron derivative 2 using cluster-chain unit 16 as a dendron core.Synthesis of Glycocluster First, glycocluster units 12 and 13 were prepared as follows. Removal of the trichloroethyl group from cluster-chain unit 3, which was prepared according to the previous paper, 9) by Zn-AcOH provided acid-free cluster-chain unit 4 (93%). Coupling of compound 4 with each w-amino acid (b-alanine and 6-aminocapronic acid) trichloroethyl ester as a spacer in the presence of diethyl phosphorocyanidate (DEPC) in dry DMF -5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan. Received March 25, 2005; accepted May 20, 2005 The synthesis of an asymmetric glycocluster 1 has been achieved using two glycocluster units 12 and 13, prepared by coupling the cluster chain unit 4 with each w w-amino acid (b b-alanine and 6-aminocapronic acid) trichloroethyl ester, and peptidic C-terminal block glycocluster 16, prepared by coupling the bifunctional linker 14 with sugar unit 9. This method facilitated the synthesis of the cluster optionally modulated the distance between the side-chain branched points by using various w w-amino acids. We also synthesized glycode...

Analysis of carbohydrates and glycoconjugates by matrix‐assisted laser desorption/ionization mass spectrometry: An update for the period 2005–2006

“…These include monosaccharides (Gao et al, 2005b;Lu, Fraser-Reid, & Gowda, 2005;Dubber et al, 2006a;Dubber, Sperling, & Lindhorst, 2006), cyclodextrins (Carpenter & Nepogodiev, 2005;Furuike et al, 2005;Gómez-García et al, 2005;Hattori et al, 2006;Yamanoi et al, 2005), calix [4]arenes (48) (ten Cate et al, 2005;Hocquelet et al, 2006), carbosilanes , phthalocyanines (49) (Alvarez-Mico et al, 2006), poly(amidoamine) (PAMAM) (Ibey et al, 2005;Kubler-Kielb & Pozsgay, 2005;Mangold et al, 2005;Wolfenden & Cloninger, 2005;Wolfenden & Cloninger, 2006;Zhu & Marchant, 2006), peptides (Hada et al, 2005;Jin et al, 2006;Kantchev, Chang, & Chang, 2006;Sato, Hada, & Takeda, 2006), pentaerythritol (2/33) (Xue et al, 2005;Al-Mughaid & Grindley, 2006), porphyrins (50) (Laville et al, 2006;Sol et al, 2006), trihydroxybenzoic acid (51) (Fernandez-Megia et al, 2006;Joosten et al, 2006), and trimesic acid (4/61) .…”

Syntheses of Model Compounds Related to an Antigenic Epitope in Pectic Polysaccharides from Bupleurum falcatum L. (II)

“…We chose the convergent approach using the bifunctional linker 25 11) as the dendron core. In this approach, a coupling reaction of 13 with dendron core 25 was carried out in the presence of DEPC to give 18 in 94% yield, which after removal of the Boc group gave dimer 19 (87%).…”

“…Meanwhile, we developed new peptidic glycoclusters and a glycodendron, which consist of a b-alanine derivative and sugar unit. [10][11][12] We report here the two types of cluster, 2 and 3, carrying trisaccharide 1 (Fig. 2) and our attempts to achieve successful augmentation through the cluster effect.…”

Syntheses of New Model Compounds Related to an Antigenic Epitope from Bupleurum falcatum L. and Their Distributions in Various Ganglioside-Phospholipid Monolayers

“…Furthermore, we developed new peptidic glycoclusters and glycodentron, 5,6) and the fluorescence-labeled…”

“…Furthermore, we developed new peptidic glycoclusters and glycodentron, 5,6) and the fluorescence-labeled cluster derivatives of b-D-GlcA4Me-(1→6)-b-D-Gal-b-DGal 7) have been synthesized for biological assay. Recently, we synthesized new glycocluster derivatives carrying double alkyl chains instead of fluorescent dansyl group.…”