Odorranalectin is a small peptide lectin with potential for drug delivery and targeting.
BACKGROUND
Lectins are sugar-binding proteins that specifically recognize sugar complexes. Based on the specificity of protein-sugar interactions, different lectins could be used as carrier molecules to target drugs specifically to different cells which express different glycan arrays. In spite of lectin's interesting biological potential for drug targeting and delivery, a potential disadvantage of natural lectins may be large size molecules that results in immunogenicity and toxicity. Smaller peptides which can mimic the function of lectins are promising candidates for drug targeting.


RESULTS
Small peptide with lectin-like behavior was screened from amphibian skin secretions and its structure and function were studied by NMR, NMR-titration, SPR and mutant analysis. A lectin-like peptide named odorranalectin was identified from skin secretions of Odorrana grahami. It was composed of 17 aa with a sequence of YASPKCFRYPNGVLACT. L-fucose could specifically inhibit the haemagglutination induced by odorranalectin. (125)I-odorranalectin was stable in mice plasma. In experimental mouse models, odorranalectin was proved to mainly conjugate to liver, spleen and lung after i.v. administration. Odorranalectin showed extremely low toxicity and immunogenicity in mice. The small size and single disulfide bridge of odorranalectin make it easy to manipulate for developing as a drug targeting system. The cyclic peptide of odorranalectin disclosed by solution NMR study adopts a beta-turn conformation stabilized by one intramolecular disulfide bond between Cys6-Cys16 and three hydrogen bonds between Phe7-Ala15, Tyr9-Val13, Tyr9-Gly12. Residues K5, C6, F7, C16 and T17 consist of the binding site of L-fucose on odorranalectin determined by NMR titration and mutant analysis. The structure of odorranalectin in bound form is more stable than in free form.


CONCLUSIONS
These findings identify the smallest lectin so far, and show the application potential of odorranalectin for drug delivery and targeting. It also disclosed a new strategy of amphibian anti-infection.
Li
Jianxu
J
Biotoxin Units of Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming Yunnan, China.
Wu
Hongbing
H
Hong
Jing
J
Xu
Xueqing
X
Yang
Hailong
H
Wu
Bingxian
B
Wang
Yipeng
Y
Zhu
Jianhua
J
Lai
Ren
R
Jiang
Xinguo
X
Lin
Donghai
D
Prescott
Mark C
MC
Rees
Huw H
HH
D000818:Animals; D001001:Anura / Q000378:metabolism*; D001419:Bacteria / Q000378:metabolism; D001483:Base Sequence; D050260:Carbohydrate Metabolism; D018076:DNA, Complementary / Q000235:genetics; D016503:Drug Delivery Systems; D005643:Fucose / Q000378:metabolism; D006384:Hemagglutination; D007457:Iodine Radioisotopes; D037102:Lectins / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D012867:Skin / Q000378:metabolism; D012996:Solutions; D013997:Time Factors; D014018:Tissue Distribution; D017186:Titrimetry
D018076:DNA, Complementary; D007457:Iodine Radioisotopes; D037102:Lectins; D010455:Peptides; D012996:Solutions; C530911:odorranalectin, Odorrana grahami; D005643:Fucose