bFGF Mutant Engineering for Enhanced Stability and Bioavailability
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Solution Overview
Problem
The stability of basic fibroblast growth factor (bFGF) is compromised due to its short half-life and susceptibility to proteases, limiting its clinical efficacy and bioavailability for use in cosmetics and pharmaceuticals.
Innovation Solution
A highly stable bFGF mutant is developed by modifying the amino acid sequence, specifically substituting cysteine residues with serine and introducing disulfide bonds to enhance thermal stability and bioavailability, while maintaining protein activity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If bFGF is used in its natural form, then it maintains biological activity for wound healing and tissue regeneration, but it has very short half-life and low stability in the body
Solution Approach 1:
The patent applies parameter changes by systematically modifying amino acid residues at specific positions (1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146) in the bFGF polypeptide chain to create mutant forms with enhanced stability and extended half-life while preserving biological activity
Solution Approach 2:
The patent applies local quality by making targeted amino acid substitutions at specific positions within the bFGF sequence rather than uniform modification throughout. Each position (1-146) can be independently modified with specific amino acids to optimize local structural properties that contribute to overall stability without compromising the global biological function
2Reliability
If bFGF is used for therapeutic purposes, then it promotes wound healing and angiogenesis, but it is susceptible to proteases which limits clinical efficacy
Solution Approach 1:
The patent modifies the protease susceptibility parameter by substituting amino acid residues that are known to be cleavage sites for proteases. This systematic parameter change at positions throughout the sequence reduces recognition and cleavage by proteolytic enzymes, thereby extending in vivo half-life and improving bioavailability
Solution Approach 2:
The patent applies preliminary anti-action by pre-modifying the bFGF sequence to resist protease degradation before administration. The amino acid substitutions are designed in advance to prevent protease binding and cleavage, creating a protease-resistant form that maintains stability during circulation and delivery to the target site
3Duration of action of stationary object
If bFGF is stored and distributed for cosmetic and pharmaceutical use, then it should maintain activity, but it has short body half-life and poor stability
Solution Approach 1:
The patent applies parameter changes by modifying amino acid residues to enhance both storage stability and in vivo half-life simultaneously. The substitutions at positions 1-146 are selected to improve structural stability for long-term storage while also extending circulation half-life, resolving the contradiction between storage durability and in vivo persistence
Solution Approach 2:
The patent applies universality by creating mutant bFGF forms that simultaneously achieve multiple functions: enhanced storage stability, extended body half-life, improved protease resistance, and maintained biological activity. The multi-functional mutant polypeptides satisfy multiple requirements that cannot be met by the native sequence alone
Data Source
AI summary
The present disclosure relates to a highly stable basic fibroblast growth factor mutant, and a use thereof. More specifically, the present disclosure provides: a highly stable basic fibroblast growth factor (bFGF) mutant, in which two or more amino acids in an amino acid sequence of SEQ ID NO: 1 are substituted with serine and one or more amino acids are substituted with cysteine; a DNA base sequence encoding the bFGF mutant; an expression vector including the DNA base sequence; a transformant transformed by the expression vector; a method of producing the bFGF mutant; and a composition including the bFGF mutant as an active ingredient. According to the present disclosure, the bFGF mutant of the present disclosure has excellent stability in an aqueous solution state and excellent thermal stability, and thus it is possible to produce functional cosmetics and skin inflammation medicines which do not lose activity, unlike conventional wild-type bFGF products, even during distribution and storage.