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Therapeutic Enzymes: Function and Clinical Implications pp 131–150Cite as

Stability of Therapeutic Enzymes: Challenges and Recent Advances

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1148))

Abstract

Enzymes are biocatalysts that have found profound applications in the current biotherapeutic industry and play a crucial role in diagnosis, prevention, and biochemical analysis of major diseases. However, stability, protein degradation and immunogenicity in the body present unique challenges that are faced upon sustained use of such enzymes. The present chapter is an attempt to dissect the state-of-the-art in relation to the challenges of development of therapeutic enzymes and the recent advances to address them. At the very outset, diseases where enzymes have found effective applications and the various causes of enzyme instability have been discussed. In recent times, polymer or nano- conjugated resistant delivery methods, as well as mutagenesis have led to manifold increase in enzyme stability against thermal denaturation, acidic gut environment, proteolysis and immunogenicity. Further, methods of analytical characterization of proteins have been highlighted and explored to shape future research directions.

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Abbreviations

US:

United States

FDA:

Food and drug administration

AML:

Acute Myeloid Leukemia

ALL:

Acute Lymphoblastic Leukemia

PEG:

Polyethylene glycol

ADP:

Adenosine Diphosphate

NAD:

Nicotinamide Adenine Dinucleotide

ERT:

Enzyme Replacement Therapy

GAG:

Glucosaminoglycans

DNA:

Deoxyribonucleic Acid

LAL:

Lysosomal Acid Lipase

MPS:

Mucopolysaccharidosis

LIPA:

Lysosomal Acid Lipase

SCID:

Severe Combined Immune Deficiency

ADA:

Adenosine Deaminase

PPFE:

Pleuroparenchymal Fibroelastosis

RNA:

Ribonucleic Acid

DUB:

Deubiquitinating Enzyme

GI:

Gastrointestinal

BAb:

Binding Antibodies

GD:

Gaucher’s Disease

GALK1:

Galactokinase 1

EC:

Enzyme Commission

ATP:

Adenosine Triphosphate

ABD:

Albumin-Binding Domain

PVP:

Poly(N-vinylpyrrolidone)

LbL:

Layer-by-layer

MNP:

Magnetic Nanoparticles

PAGE:

Poly-Acrylamide Gel Electrophoresis

SDS:

Sodium Dodecyl Sulfate

IEF:

Isoelectric Focusing

2D:

2-dimension

DIGE:

Difference Gel Electrophoresis

HPLC:

High-performance liquid chromatography

CD:

Circular Dichroism

NMR:

Nuclear Magnetic Resonance

XRD:

X-ray Diffraction

FTIR:

Fourier-Transform Infrared Spectroscopy

IR:

Infrared

DLS:

Dynamic Light Scattering

HT-DLS:

High- Throughput Dynamic Light Scattering

UVRR:

Ultraviolet Resonance Raman

ROA:

Raman Optical Activity

ANS:

8-Anilinonaphthalene-1-sulfonic acid

ThT:

Thioflavin-T

TEM:

Transmission Electron Microscopy

ELISA:

Enzyme-Linked Immunosorbent Assay

SPR:

Surface Plasmon Resonance

BLI:

Bio-Layer Interferometry

ITC:

Isothermal Titration Calorimetry

tPa:

Tissue Plasminogen Activator

SKA:

Streptokinase

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Authors and Affiliations

  1. Enzyme and Microbial Biochemistry Laboratory, Department of Chemistry, Indian Institute of Technology Delhi, New Delhi, India

    Shubhrima Ghosh, Shahenvaz Alam & S. K. Khare

  2. Department of Chemical Engineering, Indian Institute of Technology Delhi, New Delhi, India

    Anurag S. Rathore

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  1. Shubhrima Ghosh
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  2. Shahenvaz Alam
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  3. Anurag S. Rathore
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  4. S. K. Khare
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Correspondence to S. K. Khare .

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  1. Department of Biotechnology, Agricultural University of Athens, Athens, Greece

    Nikolaos Labrou

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Ghosh, S., Alam, S., Rathore, A.S., Khare, S.K. (2019). Stability of Therapeutic Enzymes: Challenges and Recent Advances. In: Labrou, N. (eds) Therapeutic Enzymes: Function and Clinical Implications. Advances in Experimental Medicine and Biology, vol 1148. Springer, Singapore. https://doi.org/10.1007/978-981-13-7709-9_7

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