Conformation for a beta-cyclodextrin monosubstituted with a cyclic dipeptide.

Abstract

The structural characterization of a (3-cyclodextrin monosubstituted with the peptide cyclo(L-HiS-L-Leu) is reported. This work provides an x-ray example of a covalently bound group that folds In such a way that the terminal apolar side chain is retained in the hydrophobic interior of the cone-shaped cyclodextrin cavity. 6-Deoxy-6-cycldo(L-histldyl-Lleucyl)-ig-cydodextrin crystallizes in the space group P 1 with cell dimensions a = 14.728 (8) Cyclodextrins (CDs) represent an interesting class of cyclic oligosaccharides constituted by 6-12 D-glucopyranosyl units, linked by a(1-4)-glycosidic bonds (1, 2). Among the known CDs, 1-CD (or cycloheptaamylose) is one of the most widely investigated so far. Crystallographic studies (3-5) have established that CDs are truncated cone-shaped cyclic molecules with glucose units in the 4C1 chair conformation. Because of the presence of the cavity and of primary hydroxyl groups, these cycloamyloses have been used for building molecular models with peculiar properties (6, 7). Furthermore, it has been shown that cyclo(L-histidyl-L-prolyl), a dipeptide with hormonal and neurotropic activity (8-13), inhibits the (Fe+ ascorbic acid)-induced peroxidation of skeletal muscle sarcoplasmic reticulum membrane lipids (14). Bavykina et al. (15) recently published the synthesis of diketopiperazines (DKPs) related to cyclo(L-histidyl-L-prolyl) and attributed the biological behavior ofthis molecule to the antioxidant activity ofthe cyclodipeptide. This suggests that DKP derivatives may be used as antiinflammatory agents (16)(17)(18)(19). In this context, we report here an example of structural characterization by x-ray diffraction analysis of a 13-CD monosubstituted with a potentially bioactive cyclic dipeptide-namely, 6-deoxy-6-cyclo(Lhistidyl-L-leucyl)-1-CD (cHL-,1CD) (Fig.

Crystal and molecular structure of β‐cyclodextrins functionalized with the anti‐inflammatory drug Etodolac

“…The total puckering amplitude Q for all residues (in the range 0.54-0.57 Å ) is slightly lower than the corresponding value found for an ideal cyclohexane chair conformation (0.63 Å ), whereas the parameter The structure reveals a ''sleeping swan''-like shape, the covalently bonded Etodolac moiety being folded with the 8-ethyl group inserted inside the hydrophobic cavity of the b-CD ring. This structure is similar in dimensions and conformation to structures we previously reported for b-CD monosubstituted with the cyclic dipeptide L-histidyl-Lleucyl 45 and with the Boc-amino-ethyl-imidazolyl moiety. 46 The functional groups assume the same type of folded conformation (with respect to the b-CD macrocycle), indicating the existence of similar host-guest binding forces between these groups and the hydrophobic cavity.…”

Carbohydrates in peptide and protein design

“…Several different types of covalent peptidecyclodextrin conjugates have been reported. Among the first were publications by Parrot-Lopez et al on the preparation of cyclodextrins singly substituted with amino acids [67][68][69] or peptides, 70 by Vecchio 76 and coworkers in 1992, Å kerfeldt and DeGrado 81 in 1994, Hanessian 79 and coworkers in 1995, Moroder 83 and coworkers and Stoddart 80 in separate publications in 1996. cyclodextrins have been used extensively in the de novo design of potential, biomimetic catalysts. However, in general, these designs do not incorporate peptides as such, with a few exceptions.…”

“…This monoamine derivative ofcyclodextrin was N-acylated with N -Boc-protected amino acids or Leu-enkephalin, which were subsequently deprotected (Figure 12). 75 In 1992 Di Blasio et al 76 reported a -cyclodextrin derivative with cyclo-(His-Pro), a diketopiperazine (DKP), covalently attached through the sidechain imidazole to C-6. X-ray studies revealed that 6-deoxy-6-cyclo-(His-Leu)--cyclodextrin was in a -Alkylated SAAs, X, Y: N 3 , CO 2 Me; N 3 , CO 2 H; NH 2 , CO 2 Me.…”

“…X-ray studies revealed that 6-deoxy-6-cyclo-(His-Leu)--cyclodextrin was in a -Alkylated SAAs, X, Y: N 3 , CO 2 Me; N 3 , CO 2 H; NH 2 , CO 2 Me. 64 ''sleeping swan''-like fold with the hydrophobic sidechain of Leu nested inside the cavity of the macrocycle, 76 i.e., self-inclusion of the grafted molecule. Self-inclusion has also been observed in another amino acid-cyclodextrin conjugate.…”

Ligand exchange capillary electrophoresis by cyclodextrin derivatives, a powerful tool for enantiomeric separations

“…In many laboratories and ours among them [18][19][20][21][22], through the required experimental effort, the synthesis of pure derivatives of CDs has been carried out. The derivatives obtained have been investigated by a plurality of spectroscopic techniques, and by pH-metric potentiometry, thermodynamic parameters concerning the protonation and the complexation of the synthesized compounds have been determined [23][24][25][26][27].…”