Adsorbents with high selectivity for uremic middle molecular peptides containing the Asp-Phe-Leu-Ala-Glu sequence.
Asp-Phe-Leu-Ala-Glu (DE5) is a frequent sequence of many toxic middle molecular peptides that accumulate in uremic patients. To eliminate these peptides by hemoperfusion, three adsorbents (CP1-Zn(2+), CP2-Zn(2+), and CP3-Zn(2+)) were designed on the basis of coordination and hydrophobic interactions. Adsorption experiments indicated that CP2-Zn(2+) had the highest affinity for DE5 among these three adsorbents. Also, the adsorption capacity of CP2-Zn(2+) in DE5 and DE5-containing peptides was about 2-6 times higher than that of peptides without the DE5 sequence. Linear polymers bearing the same functional groups of the adsorbents were used as models to study the adsorption mechanism via isothermal titration calorimetry (ITC) and computer-aided analyses. The results indicated that coordination and hydrophobic interactions played the most important roles in their affinity. When two carboxyl moieties on Asp and Glu residues coordinated to CP2-Zn(2+), the hydrophobic interaction took place by the aggregation of the hydrophobic amino acid residues with phenyl group on CP2-Zn(2+). The optimal collaboration of these interactions led to the tight binding and selective adsorption of DE5-containing peptides onto CP2-Zn(2+). These results may provide new insight into the design of affinity adsorbents for peptides containing DE5-like sequences.
Qiao
Yitao
Y
Key Laboratory of Functional Polymer Materials, Ministry of Education, College of Chemistry, Nankai University, Tianjin 300071, PR China.
Zhao
Jianxin
J
Li
Pinglin
P
Wang
Jun
J
Feng
Jing
J
Wang
Wei
W
Sun
Hongwei
H
Ma
Yi
Y
Yuan
Zhi
Z
D000327:Adsorption; D057927:Hydrophobic and Hydrophilic Interactions; D009842:Oligopeptides / Q000737:chemistry* / Q000652:urine; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D013499:Surface Properties; D014511:Uremia; D015032:Zinc / Q000737:chemistry*
D009842:Oligopeptides; D009942:Organometallic Compounds; C551341:aspartyl-phenylalanyl-leucyl-alanyl-glutamate; D015032:Zinc