Ghrelin Analog Amino Acid Substitutions for Receptor Binding
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Solution Overview
Problem
Current ghrelin analogs have limitations in terms of cell membrane binding affinity and efficiency in interacting with membrane-bound receptors, which affects their biological potency.
Innovation Solution
Ghrelin analogs with specific amino acid substitutions at residues A15, A16, A17, A18, A19, or A20, such as Asp(NH-R), Cys(S-R), or Lys(biotinyl), exhibit enhanced cell membrane binding affinity and receptor interaction, leading to increased biological potency.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If ghrelin analogs with amino acid substitutions at residues A15-A20 are designed to enhance membrane binding affinity, then biological potency is improved, but molecular structure complexity increases
Solution Approach 1:
The patent applies local quality by introducing specific amino acid substitutions (Asp(NH-R), Cys(S-R), Lys(biotinyl)) at targeted positions (A15-A20) within the ghrelin analog structure. These localized modifications enhance membrane binding affinity and biological potency without requiring complete structural redesign, thereby improving reliability while controlling complexity through focused alterations rather than global changes.
2Reliability
If ghrelin analogs are modified to increase receptor interaction efficiency, then biological activity is enhanced, but ease of manufacture decreases
Solution Approach 1:
The patent employs parameter changes by systematically varying amino acid residues at positions A15-A20 with specific substitution patterns (Asp(NH-R), Cys(S-R), Lys(biotinyl)). These controlled parameter modifications optimize receptor interaction efficiency and biological activity while maintaining a manageable structural framework that can be synthesized through established peptide chemistry methods, balancing improved reliability with reasonable ease of manufacture.
Data Source
AI summary
The invention comprises peptidyl analogs according to formulae (I) or (II) as depicted below: (R2R3)-A1-A2-A3-A4-A5-A6-A7-A8-A9-A10-A11-A12-A13-A14-A15-A16-A17-A18-A19-A20-A21-A22-A23-A24-A25-A26-A27-A28-R1 wherein the definitions of A1 to A28 and R1 to R3 are provided for in the specification for each of formulae (I) and (II), pharmaceutically acceptable salts thereof and pharmaceutical compositions comprising an effective amount of a compound of formula (I), that possess agonist or antagonist ghrelin activity, along with therapeutic and non-therapeutic uses thereof.