Engineering metalloproteinase inhibitors: tissue inhibitors of metalloproteinases or antibodies, that is the question

Kalantar, Masoud; Hilpert, Gregory A; Mosca, Ethan R; Raeeszadeh-Sarmazdeh, Maryam

doi:10.1016/j.copbio.2024.103094

Cited by 4 publications

(1 citation statement)

References 54 publications

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“…Monoclonal antibodies (mAbs) are well-established protein therapeutics generally well-tolerated by the body with minimal risk of side effects. 4 . Various antibodies have been previously used [5][6][7] and engineered [8][9][10] to target proteases, especially MMPs.…”

Section: Introductionmentioning

confidence: 99%

Elucidating key determinants of engineered scFv antibody in MMP-9 binding using high throughput screening and machine learning

Kalantar,

Kalanther,

Kumar

et al. 2024

Preprint

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An imbalance in matrix metalloproteinase-9 (MMP-9) regulation can lead to numerous diseases, including neurological disorders, cancer, and pre-term labor. Engineering single-chain antibody fragments (scFvs) Targeting MMP-9 to develop novel therapeutics for such diseases is desirable. We screened a synthetic scFv antibody library displayed on the yeast surface for binding improvement to MMP-9 using FACS (fluorescent-activated cell sorting). The scFv antibody clones isolated after FACS showed improvement in binding to MMP-9 compared to the endogenous inhibitor. To understand molecular determinants of binding between engineered scFv antibody variants and MMP-9, next-generation DNA sequencing, and computational protein structure analysis were used. Additionally, a deep-learning language model was trained on the synthetic library to predict the binding of scFv variants using their CDR-H3 sequences.

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