Special Issue "Novel Natural-based Biomolecules Discovery for Tackling Chronic Diseases"

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Natural and Bio-inspired Molecules".

Deadline for manuscript submissions: closed (30 June 2020).

Special Issue Editor

Dr. Hang Fai (Henry) Kwok
Website
Guest Editor
Faculty of Health Sciences (E12), University of Macau, Avenida de Universidade, Macau, China
Interests: Protease biochemistry; Toxins; Anti-cancer drug discovery; Antibody therapy; Venom-based peptides; Prognostic and diagnostic biomarkers; Proteomics
Special Issues and Collections in MDPI journals

Special Issue Information

Dear Colleagues,

Natural-based biomolecules continuously play an important role in novel drug discovery for treatment of chronic diseases. The development of natural peptide/protein-based, toxin-based, and antibody-based drugs can significantly improve the biomedical efficiency of disease-specific therapy.

The focus of this Special Issue of Biomolecules will be on the most recent advances related to novel peptides/proteins, antibodies, and toxins as forms of medicinal therapy. Recent advances in the discovery and development of these natural biomolecules as targeted therapy and immunotherapy for tackling chronic diseases (e.g., cancer, diabetes, cardiovascular diseases, and rheumatoid arthritis) will be addressed. The discussion on using novel disease-specific proteins/peptides/toxins/antibodies along with currently available FDA-approved drugs as combinatorial treatments will also be encouraged in this context. Finally, an overview of some selected promising natural biomolecules that are potentially able to address the forthcoming challenges in this field will be included. Both research (in particular) and review articles proposing novelties or overviews, respectively, are welcome.

Assoc. Prof. Hang Fai (Henry) Kwok


Guest Editor

Manuscript Submission Information

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Keywords

  • antibody therapy
  • peptide/protein drug
  • natural toxins
  • targeted therapy/immunotherapy for combinatorial treatment
  • cancer
  • diabetes
  • heart disease
  • inflammation

Published Papers (8 papers)

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Research

Open AccessArticle
Development and Characterization of a Fucoidan-Based Drug Delivery System by Using Hydrophilic Anticancer Polysaccharides to Simultaneously Deliver Hydrophobic Anticancer Drugs
Biomolecules 2020, 10(7), 970; https://doi.org/10.3390/biom10070970 - 28 Jun 2020
Abstract
Fucoidan, a natural sulfated polysaccharide, which can activate the immune response and lessen adverse effects, is expected to be an adjuvant agent in combination with chemotherapy. Using natural hydrophilic anticancer polysaccharides to simultaneously encapsulate hydrophobic anticancer drugs is feasible, and a reduced side [...] Read more.
Fucoidan, a natural sulfated polysaccharide, which can activate the immune response and lessen adverse effects, is expected to be an adjuvant agent in combination with chemotherapy. Using natural hydrophilic anticancer polysaccharides to simultaneously encapsulate hydrophobic anticancer drugs is feasible, and a reduced side effect can be achieved to amplify the therapeutic efficacy. In this study, a novel type of fucoidan-PLGA nanocarrier (FPN-DTX) was developed for the encapsulation of the hydrophobic anticancer drug, docetaxel (DTX), as a drug delivery system. From the comparison between FPN-DTX and the PLGA particles without fucoidan (PLGA-DTX), FPNs–DTX with fucoidan were highly stable with smaller sizes and dispersed well without aggregations in an aqueous environment. The drug loading and release can be further modified by modulating relative ratios of Fucoidan (Fu) to PLGA. The (FPN 3-DTX) nanoparticles with a 10:3 ratio of Fu:PLGA displayed uniform particle size with higher encapsulation efficiency than PLGA NPs and sustained drug release ability. The biocompatible fucoidan-PLGA nanoparticles displayed low cytotoxicity without drug loading after incubation with MDA-MB-231 triple-negative breast cancer cells. Despite lower cellular uptake than that of PLGA-DTX due to a higher degree of negative zeta potential and hydrophilicity, FPN 3-DTX effectively exerted better anticancer ability, so FPN 3-DTX can serve as a competent drug delivery system. Full article
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Open AccessArticle
Discovery of Kynurenines Containing Oligopeptides as Potent Opioid Receptor Agonists
Biomolecules 2020, 10(2), 284; https://doi.org/10.3390/biom10020284 - 12 Feb 2020
Cited by 1
Abstract
Kynurenine (kyn) and kynurenic acid (kyna) are well-defined metabolites of tryptophan catabolism collectively known as “kynurenines”, which exert regulatory functions in host-microbiome signaling, immune cell response, and neuronal excitability. Kynurenine containing peptides endowed with opioid receptor activity have been isolated from natural organisms; [...] Read more.
Kynurenine (kyn) and kynurenic acid (kyna) are well-defined metabolites of tryptophan catabolism collectively known as “kynurenines”, which exert regulatory functions in host-microbiome signaling, immune cell response, and neuronal excitability. Kynurenine containing peptides endowed with opioid receptor activity have been isolated from natural organisms; thus, in this work, novel opioid peptide analogs incorporating L-kynurenine (L-kyn) and kynurenic acid (kyna) in place of native amino acids have been designed and synthesized with the aim to investigate the biological effect of these modifications. The kyna-containing peptide (KA1) binds selectively the μ-opioid receptor with a Ki = 1.08 ± 0.26 (selectivity ratio μ/δ/κ = 1:514:10,000), while the L-kyn-containing peptide (K6) shows a mixed binding affinity for μ, δ, and κ-opioid receptors, with efficacy and potency (Emax = 209.7 + 3.4%; LogEC50 = −5.984 + 0.054) higher than those of the reference compound DAMGO. This novel oligopeptide exhibits a strong antinociceptive effect after i.c.v. and s.c. administrations in in vivo tests, according to good stability in human plasma (t1/2 = 47 min). Full article
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Open AccessArticle
Chemical Constituents of the Leaves of Butterbur (Petasites japonicus) and Their Anti-Inflammatory Effects
Biomolecules 2019, 9(12), 806; https://doi.org/10.3390/biom9120806 - 29 Nov 2019
Cited by 3
Abstract
Two new aryltetralin lactone lignans, petasitesins A and B were isolated from the hot water extract of the leaves of butterbur (Petasites japonicus) along with six known compounds. The chemical structures of lignans 1 and 2 were elucidated on the basis [...] Read more.
Two new aryltetralin lactone lignans, petasitesins A and B were isolated from the hot water extract of the leaves of butterbur (Petasites japonicus) along with six known compounds. The chemical structures of lignans 1 and 2 were elucidated on the basis of 1D and 2D nuclear magnetic resonance (NMR) spectroscopic data, electronic circular dichroism (ECD) and vibrational circular dichroism (VCD) spectra. Petasitesin A and cimicifugic acid D showed significant inhibitory effects on the production of both prostaglandin E2 (PGE2) and NO in RAW264.7 macrophages. The expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were inhibited by compound 1 in RAW264.7 cells. Furthermore, compounds 1 and 3 exhibited strong affinities with both iNOS and COX-2 enzymes in molecular docking studies. Full article
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Open AccessArticle
Identification and Isolation of Active Compounds from Astragalus membranaceus that Improve Insulin Secretion by Regulating Pancreatic β-Cell Metabolism
Biomolecules 2019, 9(10), 618; https://doi.org/10.3390/biom9100618 - 17 Oct 2019
Cited by 2
Abstract
In type 2 diabetes (T2D), insufficient secretion of insulin from the pancreatic β-cells contributes to high blood glucose levels, associated with metabolic dysregulation. Interest in natural products to complement or replace existing antidiabetic medications has increased. In this study, we examined the effect [...] Read more.
In type 2 diabetes (T2D), insufficient secretion of insulin from the pancreatic β-cells contributes to high blood glucose levels, associated with metabolic dysregulation. Interest in natural products to complement or replace existing antidiabetic medications has increased. In this study, we examined the effect of Astragalus membranaceus extract (ASME) and its compounds 19 on glucose-stimulated insulin secretion (GSIS) from pancreatic β-cells. ASME and compounds 19 isolated from A. membranaceus stimulated insulin secretion in INS-1 cells without inducing cytotoxicity. A further experiment showed that compounds 2, 3, and 5 enhanced the phosphorylation of total insulin receptor substrate-2 (IRS-2), phosphatidylinositol 3-kinase (PI3K), and Akt, and activated pancreatic and duodenal homeobox-1 (PDX-1) and peroxisome proliferator-activated receptor-γ (PPAR-γ), which are associated with β-cell function and insulin secretion. The data suggest that two isoflavonoids (2 and 3) and a nucleoside (compound 5), isolated from the roots of A. membranaceus, have the potential to improve insulin secretion in β-cells, representing the first step towards the development of potent antidiabetic drugs. Full article
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Open AccessArticle
Orientin Induces G0/G1 Cell Cycle Arrest and Mitochondria Mediated Intrinsic Apoptosis in Human Colorectal Carcinoma HT29 Cells
Biomolecules 2019, 9(9), 418; https://doi.org/10.3390/biom9090418 - 27 Aug 2019
Cited by 3
Abstract
Colorectal carcinoma is one of the utmost diagnosed cancer with a steep increase in mortality rate. The incidence has been increasing in developing countries like India due to a westernization life style. Flavonoids have been explored widely for its various pharmacological activity including [...] Read more.
Colorectal carcinoma is one of the utmost diagnosed cancer with a steep increase in mortality rate. The incidence has been increasing in developing countries like India due to a westernization life style. Flavonoids have been explored widely for its various pharmacological activity including antitumor activity. Orientin, an analogue of luteolin (citrus flavonoid) isolated from rooibos and tulsi leaves is also expected to deliver significant antitumor activity similar to that of luteolin. The present study anticipates exploring the antitumor activity of orientin against colorectal carcinoma cells (HT29). Orientin exhibited remarkable cytotoxicity and antiproliferative activity against HT29 cells, which is clearly evident from tetrazolium based cytotoxicity and lactate dehydrogenase release assays. Orientin induce G0/G1 cell cycle arrest and regulates cyclin and cyclin-dependent protein kinases in order to prevent the entry of the cell cycle to the S phase. Annexin V-FITC (V-Fluorescein Isothiocyanate) dual staining reveals the apoptotic induction ability of orientin. The Bcl-2 family proteins along with the inhibitor of apoptotic proteins were regulated and the tumor suppressor p-53 expression have been decreased. In conclusion, our results proposed that orientin could be a potent chemotherapeutic agent against colorectal cancer after ascertaining their molecular mechanisms. Full article
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Open AccessArticle
The Natural-Based Antitumor Compound T21 Decreases Survivin Levels through Potent STAT3 Inhibition in Lung Cancer Models
Biomolecules 2019, 9(8), 361; https://doi.org/10.3390/biom9080361 - 13 Aug 2019
Cited by 3
Abstract
Lung cancer is the leading cause of cancer-related deaths worldwide; hence novel treatments for this malignancy are eagerly needed. Since natural-based compounds represent a rich source of novel chemical entities in drug discovery, we have focused our attention on tambjamines, natural compounds isolated [...] Read more.
Lung cancer is the leading cause of cancer-related deaths worldwide; hence novel treatments for this malignancy are eagerly needed. Since natural-based compounds represent a rich source of novel chemical entities in drug discovery, we have focused our attention on tambjamines, natural compounds isolated from marine invertebrates that have shown diverse pharmacological activities. Based on these structures, we have recently identified the novel indole-based tambjamine analog 21 (T21) as a promising antitumor agent, which modulates the expression of apoptotic proteins such as survivin. This antiapoptotic protein plays an important role in carcinogenesis and chemoresistance. In this work, we have elucidated the molecular mechanism by which the anticancer compound T21 exerts survivin inhibition and have validated this protein as a therapeutic target in different lung cancer models. T21 was able to reduce survivin protein levels in vitro by repressing its gene expression through the blockade of Janus kinase/Signal Transducer and Activator of Transcription-3 (JAK/STAT3)/survivin signaling pathway. Interestingly, this occurred even when the pathway was overstimulated with its ligand interleukin 6 (IL-6), which is frequently overexpressed in lung cancer patients who show poor clinical outcomes. Altogether, these results show T21 as a potent anticancer compound that effectively decreases survivin levels through STAT3 inhibition in lung cancer, appearing as a promising therapeutic drug for cancer treatment. Full article
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Open AccessArticle
Discovery and Rational Design of a Novel Bowman-Birk Related Protease Inhibitor
Biomolecules 2019, 9(7), 280; https://doi.org/10.3390/biom9070280 - 14 Jul 2019
Cited by 1
Abstract
Anuran amphibian skin secretions are a rich source of peptides, many of which represent novel protease inhibitors and can potentially act as a source for protease inhibitor drug discovery. In this study, a novel bioactive Bowman-Birk type inhibitory hexadecapeptide of the Ranacyclin family [...] Read more.
Anuran amphibian skin secretions are a rich source of peptides, many of which represent novel protease inhibitors and can potentially act as a source for protease inhibitor drug discovery. In this study, a novel bioactive Bowman-Birk type inhibitory hexadecapeptide of the Ranacyclin family from the defensive skin secretion of the Fukien gold-striped pond frog, Pelophlax plancyi fukienesis, was successfully isolated and identified, named PPF-BBI. The primary structure of the biosynthetic precursor was deduced from a cDNA sequence cloned from a skin-derived cDNA library, which contains a consensus motif representative of the Bowman-Birk type inhibitor. The peptide was chemically synthesized and displayed a potent inhibitory activity against trypsin (Ki of 0.17 µM), as well as an inhibitory activity against tryptase (Ki of 30.73 µM). A number of analogues of this peptide were produced by rational design. An analogue, which substituted the lysine (K) at the predicted P1 position with phenylalanine (F), exhibited a potent chymotrypsin inhibitory activity (Ki of 0.851 µM). Alternatively, a more potent protease inhibitory activity, as well as antimicrobial activity, was observed when P16 was replaced by lysine, forming K16-PPF-BBI. The addition of the cell-penetrating peptide Tat with a trypsin inhibitory loop resulted in a peptide with a selective inhibitory activity toward trypsin, as well as a strong antifungal activity. This peptide also inhibited the growth of two lung cancer cells, H460 and H157, demonstrating that the targeted modifications of this peptide could effectively and efficiently alter its bioactivity. Full article
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Open AccessArticle
Regulation of the Expression of DAPK1 by SUMO Pathway
Biomolecules 2019, 9(4), 151; https://doi.org/10.3390/biom9040151 - 17 Apr 2019
Cited by 1
Abstract
Death Associated Protein Kinase 1 (DAPK1) is an important signaling kinase mediating the biological effect of multiple natural biomolecules such as IFN-γ, TNF-α, curcumin, etc. DAPK1 is degraded through both ubiquitin-proteasomal and lysosomal degradation pathways. To investigate the crosstalk between these two DAPK1 [...] Read more.
Death Associated Protein Kinase 1 (DAPK1) is an important signaling kinase mediating the biological effect of multiple natural biomolecules such as IFN-γ, TNF-α, curcumin, etc. DAPK1 is degraded through both ubiquitin-proteasomal and lysosomal degradation pathways. To investigate the crosstalk between these two DAPK1 degradation pathways, we carried out a screen using a set of ubiquitin E2 siRNAs at the presence of Tuberous Sclerous 2 (TSC2) and identified that the small ubiquitin-like molecule (SUMO) pathway is able to regulate the protein levels of DAPK1. Inhibition of the SUMO pathway enhanced DAPK1 protein levels and the minimum domain of DAPK1 protein required for this regulation is the kinase domain, suggesting that the SUMO pathway regulates DAPK1 protein levels independent of TSC2. Suppression of the SUMO pathway did not enhance DAPK1 protein stability. In addition, mutation of the potential SUMO conjugation sites on DAPK1 kinase domain did not alter its protein stability or response to SUMO pathway inhibition. These data suggested that the SUMO pathway does not regulate DAPK1 protein degradation. The exact molecular mechanism underlying this regulation is yet to be discovered. Full article
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