Synthesis and biological evaluation of modified laminin peptide (N2S2-KDP) with enhanced affinity for neuronal growth and targeted molecular imaging (SPECT).
Bioorg Chem
; 107: 104516, 2021 02.
Article
em En
| MEDLINE
| ID: mdl-33293057
ABSTRACT
An analog of γ1 laminin (RDIAEIIKDI) decapeptide has been used to augment neuronal survival and regeneration after injuries, during aging and other CNS disorder. As a prime synthetic peptide, KDI, is responsible for the neurite outgrowth of human embryonic neurons. In this study, we have designed, modified a KDI derivative and synthesized by replacing isoleucine (I) with Pro (P) amino acid at C-terminal to enhance its potency towards neurite growth. -Cys-Gly-Cys (-CGC) N2S2 motif was also incorporated in the present design for peptide radiolabeling. The modified peptide showed a better binding with the desired 3T1M receptor for neurite growth. The peptide was synthesized using solid phase peptide synthesis and Fmoc-strategy with more than 80% yield. The receptor binding studies of 99mTc-N2S2-KDP in Neuro2A cell lines showed Kd value in 31 nM range and the complex showed appreciable brain uptake in mice. The results on human SH-SY5Y indicate that the unlabeled N2S2-KDP may perhaps be useful for neurite growth in neurodegenerative disorder.
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Base de dados:
MEDLINE
Assunto principal:
Laminina
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Compostos Radiofarmacêuticos
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Crescimento Neuronal
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Neurônios
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article