Just how prevalent are peptide therapeutic products? A critical review

Zhang, Yajie; Zhang, Hairui; Ghosh, Debadyuti; Williams, Robert O.

doi:10.1016/j.ijpharm.2020.119491

Cited by 32 publications

(28 citation statements)

References 135 publications

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“…There is growing acceptance of peptides and peptidomimetics as therapeutic drugs. As of 2020, over 70 peptide drugs have been approved by FDA, and over 160 peptides are currently in clinical testing in various disease settings (Lau & Dunn, 2018; Zhang et al, 2020). There were 13 new tailor‐made amino acids‐derived pharmaceuticals gained FDA approval in 2019 (Yin et al, 2020).…”

Section: Current Status and Challenges For Moving Pdc To Clinicmentioning

confidence: 99%

Brain penetrating peptides and peptide–drug conjugates to overcome the blood–brain barrier and target CNS diseases

Zhou

Smith

Liu

2021

WIREs Nanomed Nanobiotechnol

113

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Nearly one in six people worldwide suffer from disorders of the central nervous system (CNS). There is an urgent need for effective strategies to improve the success rates in CNS drug discovery and development. The lack of effective technologies for delivering drugs and genes to the brain due to the blood–brain barrier (BBB), a structural barrier that effectively blocks most neurotherapeutic agents from reaching the brain, has posed a formidable hurdle for CNS drug development. Brain‐homing and brain‐penetrating molecular transport vectors, such as brain permeable peptides or BBB shuttle peptides, have shown promise in overcoming the BBB and ferrying the drug molecules to the brain. The BBB shuttle peptides are discovered by phage display technology or derived from natural neurotropic proteins or certain viruses and harness the receptor‐mediated transcytosis molecular machinery for crossing the BBB. Brain permeable peptide–drug conjugates (PDCs), composed of BBB shuttle peptides, linkers, and drug molecules, have emerged as a promising CNS drug delivery system by taking advantage of the endogenous transcytosis mechanism and tricking the brain into allowing these bioactive molecules to pass the BBB. Here, we examine the latest development of brain‐penetrating peptide shuttles and brain‐permeable PDCs as molecular vectors to deliver small molecule drug payloads across the BBB to reach brain parenchyma. Emerging knowledge of the contribution of the peptides and their specific receptors expressed on the brain endothelial cells, choice of drug payloads, the design of PDCs, brain entry mechanisms, and delivery efficiency to the brain are highlighted. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Therapeutic Approaches and Drug Discovery > Nanomedicine for Neurological Disease

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Section: Current Status and Challenges For Moving Pdc To Clinicmentioning

confidence: 99%

Brain penetrating peptides and peptide–drug conjugates to overcome the blood–brain barrier and target CNS diseases

Zhou

Smith

Liu

2021

WIREs Nanomed Nanobiotechnol

113

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“…In spite of their advantages, peptide therapeutics represent an exceedingly small fraction of all approved therapeutics, with only 70 compounds approved in the U.S., Europe and Japan as of 2020 1 . In practice, oral delivery of peptide therapeutics remains a sizable challenge due to their low bioavailability caused by the presence of proteases in the gastrointestinal tract, and size and charge constraints associated with the permeability of the mucosal membrane of the gut, among others 2 .…”

Section: Introductionmentioning

confidence: 99%

Assessing sequence-based protein–protein interaction predictors for use in therapeutic peptide engineering

Charih

Biggar

Green

2022

Sci Rep

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Engineering peptides to achieve a desired therapeutic effect through the inhibition of a specific target activity or protein interaction is a non-trivial task. Few of the existing in silico peptide design algorithms generate target-specific peptides. Instead, many methods produce peptides that achieve a desired effect through an unknown mechanism. In contrast with resource-intensive high-throughput experiments, in silico screening is a cost-effective alternative that can prune the space of candidates when engineering target-specific peptides. Using a set of FDA-approved peptides we curated specifically for this task, we assess the applicability of several sequence-based protein–protein interaction predictors as a screening tool within the context of peptide therapeutic engineering. We show that similarity-based protein–protein interaction predictors are more suitable for this purpose than the state-of-the-art deep learning methods publicly available at the time of writing. We also show that this approach is mostly useful when designing new peptides against targets for which naturally-occurring interactors are already known, and that deploying it for de novo peptide engineering tasks may require gathering additional target-specific training data. Taken together, this work offers evidence that supports the use of similarity-based protein–protein interaction predictors for peptide therapeutic engineering, especially peptide analogs.

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“…The global peptide therapeutics market is one of the fastest growing segments of the pharmaceutical industry right now, with the market valued at USD 20 billion in 2017 and expected to gain USD 50 billion in revenues by 2024 [ 1 ]. Compared to small molecule drugs, peptides have greater efficacy, selectivity, and specificity, with lower risks of systemic toxicity and complications.…”

Section: Introductionmentioning

confidence: 99%

Charge-Sensitive Optical Detection of Binding Kinetics between Phage-Displayed Peptide Ligands and Protein Targets

Liang

Zhang²,

et al. 2022

Biosensors

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Phage display technology has been a powerful tool in peptide drug development. However, the supremacy of phage display-based peptide drug discovery is plagued by the follow-up process of peptides synthesis, which is costly and time consuming, but is necessary for the accurate measurement of binding kinetics in order to properly triage the best peptide leads during the affinity maturation stages. A sensitive technology is needed for directly measuring the binding kinetics of peptides on phages to reduce the time and cost of the entire process. Here, we show the capability of a charge-sensitive optical detection (CSOD) method for the direct quantification of binding kinetics of phage-displayed peptides to their target protein, using whole phages. We anticipate CSOD will contribute to streamline the process of phage display-based drug discovery.

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Just how prevalent are peptide therapeutic products? A critical review

Cited by 32 publications

References 135 publications

Brain penetrating peptides and peptide–drug conjugates to overcome the blood–brain barrier and target CNS diseases

Brain penetrating peptides and peptide–drug conjugates to overcome the blood–brain barrier and target CNS diseases

Assessing sequence-based protein–protein interaction predictors for use in therapeutic peptide engineering

Charge-Sensitive Optical Detection of Binding Kinetics between Phage-Displayed Peptide Ligands and Protein Targets

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