Eglins b/c
Cysteine-free serine protease inhibitors with anti-inflammatory and neurotrophic properties
Last updated: March 14, 2026
Mechanism Disclaimer
Eglins b and c are compact serine protease inhibitors originally isolated from Hirudo medicinalis salivary gland secretion. At 8,073 Da (eglin b) and 8,099 Da (eglin c), they differ by a single amino acid substitution at position 35 (His in eglin b, Tyr in eglin c). With 70 amino acids and no cysteine residues, eglins are uniquely devoid of disulfide bonds among leech proteinase inhibitors — a feature that contributes to exceptional thermal and acid stability.
Structural Characteristics
Potato Inhibitor I Family
Eglins belong to the potato inhibitor I (PI-1) superfamily, sharing structural homology with barley chymotrypsin inhibitor CI-2. This plant-origin fold in an animal protease inhibitor suggests ancient evolutionary convergence. The absence of disulfide bonds renders eglins resistant to reducing environments and simplifies recombinant production.
Single-Residue Difference
Eglin b (His35) and eglin c (Tyr35) are otherwise identical in sequence and exhibit overlapping but non-identical inhibitory profiles. Eglin c has been more extensively characterized due to its early successful expression in E. coli (Rink et al., 1984) — one of the first leech proteins produced recombinantly.
Inhibitory Profile
| Target Protease | Ki | Significance |
|---|---|---|
| Neutrophil elastase | 2 × 10⁻¹⁰ M | Sub-nanomolar; blocks tissue destruction |
| Cathepsin G | 2.8 × 10⁻¹⁰ M | Key neutrophil serine protease |
| Mast cell chymase | 4.45 × 10⁻⁸ M | Moderate; LDTI more potent for mast cells |
| α-Chymotrypsin | Nanomolar range | Broad serine protease activity |
| Subtilisin | Nanomolar range | Bacterial serine protease |
Anti-Inflammatory Significance
The primary therapeutic interest in eglins centers on their ability to block neutrophil-mediated tissue destruction. During inflammatory responses, activated neutrophils release elastase and cathepsin G from azurophilic granules. Uncontrolled release of these proteases degrades extracellular matrix components (elastin, collagen, proteoglycans) and amplifies inflammatory cascades. Eglins inhibit both enzymes at sub-nanomolar concentrations, positioning them as potential modulators of tissue damage in:
Rheumatoid Arthritis
Synovial neutrophil infiltration
COPD
Elastase-driven alveolar destruction
ARDS
Neutrophilic pulmonary inflammation
Additional Biological Activities
Neurotrophic Activity
Eglin c demonstrates significant neurite outgrowth stimulation in chick embryo dorsal root ganglia, with a 48.3% increase in explant area index (EAI) at a concentration of 0.1 ng/mL (Chapter 7). This places eglins among the biologically active SGS components with dual anti-inflammatory and neurotrophic properties.
HCV NS3 Proteinase Inhibition
Martin et al. (1998) demonstrated that eglin c inhibits the hepatitis C virus NS3 serine proteinase at nanomolar concentrations. Although not pursued therapeutically, this finding illustrates the broad-spectrum serine protease inhibitory capacity of the eglin scaffold.
Piyavit Component
Eglins are constituent components of Piyavit, a pharmaceutical formulation derived from whole leech extract. Their presence contributes to the immunomodulatory properties attributed to the formulation, including anti-inflammatory effects on neutrophil-mediated tissue damage pathways.
Recombinant Production
Rink et al. (1984) achieved the first heterologous expression of eglin c in E. coli, producing active protein in high yields. The absence of disulfide bonds and glycosylation sites makes eglins particularly amenable to bacterial expression — a significant advantage for scale-up.