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      Natural Peptides in Drug Discovery Targeting Acetylcholinesterase

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          Abstract

          Acetylcholinesterase-inhibitory peptide has gained much importance since it can inhibit acetylcholinesterase (AChE) and increase the availability of acetylcholine in cholinergic synapses, enhancing cholinergic transmission in pharmacological treatment of Alzheimer’s disease (AD). Natural peptides have received considerable attention as biologically important substances as a source of AChE inhibitors. These natural peptides have high potential pharmaceutical and medicinal values due to their bioactivities as neuroprotective and neurodegenerative treatment activities. These peptides have attracted great interest in the pharmaceutical industries, in order to design potential peptides for use in the prophylactic and therapy purposes. Some natural peptides and their derivatives have high commercial values and have succeeded in reaching the pharmaceutical market. A large number of peptides are already in preclinical and clinical pipelines for treatment of various diseases. This review highlights the recent researches on the various natural peptides and future prospects for AD management.

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          Most cited references138

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          The future of peptide-based drugs.

          The suite of currently used drugs can be divided into two categories - traditional 'small molecule' drugs with typical molecular weights of 5000 Da that are not orally bioavailable and need to be delivered via injection. Due to their small size, conventional small molecule drugs may suffer from reduced target selectivity that often ultimately manifests in human side-effects, whereas protein therapeutics tend to be exquisitely specific for their targets due to many more interactions with them, but this comes at a cost of low bioavailability, poor membrane permeability, and metabolic instability. The time has now come to reinvestigate new drug leads that fit between these two molecular weight extremes, with the goal of combining advantages of small molecules (cost, conformational restriction, membrane permeability, metabolic stability, oral bioavailability) with those of proteins (natural components, target specificity, high potency). This article uses selected examples of peptides to highlight the importance of peptide drugs, some potential new opportunities for their exploitation, and some difficult challenges ahead in this field. © 2012 John Wiley & Sons A/S.
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            Tat peptide-derivatized magnetic nanoparticles allow in vivo tracking and recovery of progenitor cells.

            The ability to track the distribution and differentiation of progenitor and stem cells by high-resolution in vivo imaging techniques would have significant clinical and research implications. We have developed a cell labeling approach using short HIV-Tat peptides to derivatize superparamagnetic nanoparticles. The particles are efficiently internalized into hematopoietic and neural progenitor cells in quantities up to 10-30 pg of superparamagnetic iron per cell. Iron incorporation did not affect cell viability, differentiation, or proliferation of CD34+ cells. Following intravenous injection into immunodeficient mice, 4% of magnetically CD34+ cells homed to bone marrow per gram of tissue, and single cells could be detected by magnetic resonance (MR) imaging in tissue samples. In addition, magnetically labeled cells that had homed to bone marrow could be recovered by magnetic separation columns. Localization and retrieval of cell populations in vivo enable detailed analysis of specific stem cell and organ interactions critical for advancing the therapeutic use of stem cells.
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              Twenty years of cell-penetrating peptides: from molecular mechanisms to therapeutics

              The recent discovery of new potent therapeutic molecules that do not reach the clinic due to poor delivery and low bioavailability have made of delivery a key stone in therapeutic development. Several technologies have been designed to improve cellular uptake of therapeutic molecules, including cell-penetrating peptides (CPPs). CPPs were first discovered based on the potency of several proteins to enter cells. Numerous CPPs have been described so far, which can be grouped into two major classes, the first requiring chemical linkage with the drug for cellular internalization and the second involving formation of stable, non-covalent complexes with drugs. Nowadays, CPPs constitute very promising tools for non-invasive cellular import of cargo and have been successfully applied for in vitro and in vivo delivery of therapeutic molecules varying from small chemical molecule, nucleic acids, proteins, peptides, liposomes and particles. This review will focus on the structure/function and cellular uptake mechanism of CPPs in the general context of drug delivery. We will also highlight the application of peptide carriers for the delivery of therapeutic molecules and provide an update of their clinical evaluation. This article is part of a themed section on Vector Design and Drug Delivery. For a list of all articles in this section see the end of this paper, or visit: http://www3.interscience.wiley.com/journal/121548564/issueyear?year=2009
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                Author and article information

                Journal
                Molecules
                Molecules
                molecules
                Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry
                MDPI
                1420-3049
                13 September 2018
                September 2018
                : 23
                : 9
                : 2344
                Affiliations
                [1 ]Faculty of Biotechnology, Atma Jaya Catholic University of Indonesia, Jakarta 12930, Indonesia; vivitri.dewi@ 123456atmajaya.ac.id
                [2 ]Department of Medical Laboratory Technology, Academy of Health Sciences Guna Bangsa, Condongcatur, Depok, Sleman, Yogyakarta 55283, Indonesia; radifar@ 123456gunabangsa.ac.id
                [3 ]Faculty of Pharmacy, Sanata Dharma University, Paingan, Maguwoharjo, Depok, Sleman, Yogyakarta 55282, Indonesia
                Author notes
                [* ]Correspondence: enade@ 123456usd.ac.id ; Tel.: +62-274-883037
                Author information
                https://orcid.org/0000-0002-2992-1247
                https://orcid.org/0000-0001-9156-9478
                https://orcid.org/0000-0002-8344-5587
                Article
                molecules-23-02344
                10.3390/molecules23092344
                6225273
                30217053
                42479ff4-7593-44de-b1e5-60ba8594c1e8
                © 2018 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 28 July 2018
                : 12 September 2018
                Categories
                Review

                natural peptides,acetylcholinesterase,drug discovery,inhibitor,alzheimer’s disease

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