Why structurally different cyclic peptides can be glycomimetics of the HNK-1 carbohydrate antigen.
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Why structurally different cyclic peptides can be glycomimetics of the HNK-1 carbohydrate antigen. / Bhunia, Anirban; Vivekanandan, Subramanian; Eckert, Thomas; Burg-Roderfeld, Monika; Wechselberger, Rainer; Romanuka, Julija; Bächle, Dirk; Kornilov, Andrei V; von der Lieth, Claus-Wilhelm; Jiménez-Barbero, Jesús; Nifantiev, Nikolay E; Schachner, Melitta; Sewald, Norbert; Lütteke, Thomas; Hans-Joachim, Gabius; Siebert, Hans-Christian.
In: J AM CHEM SOC, Vol. 132, No. 1, 1, 2010, p. 96-105.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Why structurally different cyclic peptides can be glycomimetics of the HNK-1 carbohydrate antigen.
AU - Bhunia, Anirban
AU - Vivekanandan, Subramanian
AU - Eckert, Thomas
AU - Burg-Roderfeld, Monika
AU - Wechselberger, Rainer
AU - Romanuka, Julija
AU - Bächle, Dirk
AU - Kornilov, Andrei V
AU - von der Lieth, Claus-Wilhelm
AU - Jiménez-Barbero, Jesús
AU - Nifantiev, Nikolay E
AU - Schachner, Melitta
AU - Sewald, Norbert
AU - Lütteke, Thomas
AU - Hans-Joachim, Gabius
AU - Siebert, Hans-Christian
PY - 2010
Y1 - 2010
N2 - 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.
AB - 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.
M3 - SCORING: Zeitschriftenaufsatz
VL - 132
SP - 96
EP - 105
JO - J AM CHEM SOC
JF - J AM CHEM SOC
SN - 0002-7863
IS - 1
M1 - 1
ER -