title: Why structurally different cyclic peptides can be glycomimetics of the HNK-1 carbohydrate antigen.
abstract: The cyclic peptides c-(LSETTl) and c-(RTLPFS) are of potential clinical interest--they stimulate neurite outgrowth in a way that is similar to the effects of the HNK-1 (human natural killer cell-1) antigenic carbohydrate chains, which are terminated by 3'-sulfated glucuronic acid attached to an N-acetyllactosamine unit. To investigate the structure-activity relationships of the ability of the cyclic peptides to mimic HNK-1 carbohydrates, conformational analysis and examination of hydrophobic and hydrophilic patterns were performed and compared with the characteristics of a synthetic HNK-1 trisaccharide derivative. Data obtained demonstrate that both the trisaccharide and the glycomimetic peptide c-(LSETTl) exhibit a similar relationship between their hydrophobic moieties and their negatively charged sites. However, the second cyclic glycomimetic peptide investigated here, c-(RTLPFS), has a positively charged group as a potential contact point due to its Arg residue. Therefore, we studied the amino acid composition of all known receptor structures in the Protein Data Bank that are in contact with uronic acid and/or sulfated glycans. Interactions of the HNK-1 trisaccharide, c-(LSETTl), and c-(RTLPFS) with a laminin fragment involved in HNK-1 carbohydrate binding (i.e., the 21mer peptide: KGVSSRSYVGCIKNLEISRST) were also analyzed. Because the structure of the HNK-1-binding laminin domain is not available in the Protein Data Bank, we used the HNK-1-binding 21mer peptide fragment of laminin for the construction of a model receptor that enabled us to compare the molecular interplay of the HNK-1 trisaccharide and the two cyclopeptides c-(LSETTl) and c-(RTLPFS) with a reliable receptor structure in considerable detail.
authors: Institut für Biochemie und Endokrinologie, Veterinrmedizinische Fakultät, Justus-Liebig-Universität Giessen, Frankfurter Str. 100, 35392 Giessen, Germany.
authors: Anirban
authors: A
authors: Bhunia
authors: Subramanian
authors: S
authors: Vivekanandan
authors: Thomas
authors: T
authors: Eckert
authors: Monika
authors: M
authors: Burg-Roderfeld
authors: Rainer
authors: R
authors: Wechselberger
authors: Julija
authors: J
authors: Romanuka
authors: Dirk
authors: D
authors: Bächle
authors: Andrei V
authors: AV
authors: Kornilov
authors: Claus-Wilhelm
authors: CW
authors: von der Lieth
authors: Jesús
authors: J
authors: Jiménez-Barbero
authors: Nikolay E
authors: NE
authors: Nifantiev
authors: Melitta
authors: M
authors: Schachner
authors: Norbert
authors: N
authors: Sewald
authors: Thomas
authors: T
authors: Lütteke
authors: Gabius
authors: G
authors: Hans-Joachim
authors: Hans-Christian
authors: HC
authors: Siebert
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D000941:Antigens / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D002236:Carbohydrate Conformation; D050260:Carbohydrate Metabolism; D002241:Carbohydrates / Q000737:chemistry*; D019295:Computational Biology; D004121:Dimethyl Sulfoxide / Q000737:chemistry; D006801:Humans; D007694:Killer Cells, Natural; D007797:Laminin / Q000737:chemistry / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D056004:Molecular Dynamics Simulation; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D014574:Uronic Acids / Q000737:chemistry; D014867:Water / Q000737:chemistry
chemical_list: D000941:Antigens; D002241:Carbohydrates; D007797:Laminin; D010456:Peptides, Cyclic; D014574:Uronic Acids; D014867:Water; D004121:Dimethyl Sulfoxide