Characterization of linear mimetic peptides of Interleukin-22 from dissection of protein interfaces

Manna, Sara La; Scognamiglio, Pasqualina Liana; Natale, Concetta Di; Leone, Marilisa; Mercurio, Flavia Anna; Malfitano, Anna Maria; Cianfarani, Francesca; Madonna, Stefania; Caravella, Sergio; Albanesi, Cristina; Novellino, Ettore; Marasco, Daniela

doi:10.1016/j.biochi.2017.05.002

Cited by 16 publications

(15 citation statements)

References 57 publications

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“…CD spectra of SOCS3 peptides were recorded in the far UV region in 10 mM phosphate buffer and in the presence of a structuring agent like TFE 42,43 (Fig. 2).…”

Section: Circular Dichroismmentioning

confidence: 99%

Mimetics of suppressor of cytokine signaling 3: Novel potential therapeutics in triple breast cancer

Manna

Lee

Ouzounova

et al. 2018

Intl Journal of Cancer

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Suppressor of cytokine signaling (SOCS) family of proteins plays critical role in the regulation of immune responses controlling JAK/STAT mediated inflammatory cytokines. Among the members, SOCS1 and SOCS3 contain a kinase inhibitory region (KIR) and SOCS3 binds to JAK/STAT/gp130 complex by inhibiting the downstream signaling and suppressing inflammatory cytokines. Loss or reduced levels of SOCS3 have been linked to cancer-associated inflammation and suppressive immunity leading to enhanced tumor growth and metastasis. In line with these reports, we previously demonstrated that proteolytic degradation of SOCS3 in triple negative breast cancer (TNBC) subtype drives the expression of inflammatory cytokines. Therefore, we postulated that SOCS3 mimetics might suppress the inflammatory cytokine production in TNBC subtype and inhibit tumor growth and metastasis. Here we designed and characterized five linear peptides derived from the N-terminal region of SOCS3 encompassing regions that interface with the JAK2/gp130 complex using the Circular Dichroism and Surface Plasmon Resonance spectroscopies. The KIRESS peptide resulted the sequence containing the most part of the hot-spots required for binding to JAK2 and was further investigated in vivo in mouse xenografts of MDA-MB-231-luci tumors as models of human TNBC subtype. Expectedly, this peptide showed a significant inhibition of primary tumor growth and pulmonary metastasis. Our studies suggest that SOCS3 peptidomimetics may possess a therapeutic potential in aggressive cancers, such as TNBC subtype, with activated inflammatory cytokines.

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“…CD spectra of SOCS3 peptides were recorded in the far UV region in 10 mM phosphate buffer and in the presence of a structuring agent like TFE 42,43 (Fig. 2).…”

Section: Circular Dichroismmentioning

confidence: 99%

Mimetics of suppressor of cytokine signaling 3: Novel potential therapeutics in triple breast cancer

Manna

Lee

Ouzounova

et al. 2018

Intl Journal of Cancer

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“…Unfortunately, high toxicity, low selectivity, and a wide range of undesired side-effects are associated with them, including brain–blood barrier cross and the generation of toxic molecules after metabolic process; they are often inadequate in long therapy [ 7 ] ( Figure 1 ). An alternative treatment, based on the use of bioactive peptides as anti-inflammatory agents, is being developed [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Peptides as Therapeutic Agents for Inflammatory-Related Diseases

Manna

Natale

Florio

et al. 2018

IJMS

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Inflammation is a physiological mechanism used by organisms to defend themselves against infection, restoring homeostasis in damaged tissues. It represents the starting point of several chronic diseases such as asthma, skin disorders, cancer, cardiovascular syndrome, arthritis, and neurological diseases. An increasing number of studies highlight the over-expression of inflammatory molecules such as oxidants, cytokines, chemokines, matrix metalloproteinases, and transcription factors into damaged tissues. The treatment of inflammatory disorders is usually linked to the use of unspecific small molecule drugs that can cause undesired side effects. Recently, many efforts are directed to develop alternative and more selective anti-inflammatory therapies, several of them imply the use of peptides. Indeed, peptides demonstrated as elected lead compounds toward several targets for their high specificity as well as recent and innovative synthetic strategies. Several endogenous peptides identified during inflammatory responses showed anti-inflammatory activities by inhibiting, reducing, and/or modulating the expression and activity of mediators. This review aims to discuss the potentialities and therapeutic use of peptides as anti-inflammatory agents in the treatment of different inflammation-related diseases and to explore the importance of peptide-based therapies.

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“…Tumor growth and development is dramatically increased by the presence of inflammatory cells; inflammatory mediators are considered a tumor microenvironment [26,27]. Recently, cancer treatments based on the application of synthesized peptides as anti-inflammatory agents have been used [28].…”

Section: Introductionmentioning

confidence: 99%

Anticancer Activities of Newly Synthesized Chiral Macrocyclic Heptapeptide Candidates

et al. 2020

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As important cancer therapeutic agents, macrocyclic peptides have recently drawn great attention, mainly because they are synthetically accessible and have lower toxicity towards normal cells. In the present work, we synthesized newly macrocyclic pyridoheptapeptide derivatives. The synthesized derivatives were characterized using standard chemical and spectroscopic analytical techniques, and their anticancer activities against human breast and hepatocellular cancer cells were investigated. Results showed that compounds 1a and 1b were the most effective against hepatocellular (HepG2) and breast (MCF-7) cancer cell lines, respectively.

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Characterization of linear mimetic peptides of Interleukin-22 from dissection of protein interfaces

Cited by 16 publications

References 57 publications

Mimetics of suppressor of cytokine signaling 3: Novel potential therapeutics in triple breast cancer

Mimetics of suppressor of cytokine signaling 3: Novel potential therapeutics in triple breast cancer

Peptides as Therapeutic Agents for Inflammatory-Related Diseases

Anticancer Activities of Newly Synthesized Chiral Macrocyclic Heptapeptide Candidates

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