Multidimensional Design of Anticancer Peptides

Lin, Yen‐Chu; Lim, Yi Fan; Russo, Erica; Schneider, Petra; Bolliger, Lea; Edenharter, Adriana; Altmann, Karl‐Heinz; Hiss, Jan A.

doi:10.1002/anie.201504018

Cited by 35 publications

(20 citation statements)

References 35 publications

(45 reference statements)

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“…However, delivery of other classes of cargoes, including proteins, peptides, PNA, PMO, and others will benefit from improvements in CPP efficiency in vitro and in vivo. Further, the field will benefit from new processes for rapidly improving upon known CPPs, building on some successes in screening and algorithm-aided design 43 , 44 .…”

Section: Discussionmentioning

confidence: 99%

Synthetic molecular evolution of hybrid cell penetrating peptides

2018

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Peptides and analogs such as peptide nucleic acids (PNA) are promising tools and therapeutics, but the cell membrane remains a barrier to intracellular targets. Conjugation to classical cell penetrating peptides (CPPs) such as pTat48–60 (tat) and pAntp43–68 (penetratin) facilitates delivery; however, efficiencies are low. Lack of explicit design principles hinders rational improvement. Here, we use synthetic molecular evolution (SME) to identify gain-of-function CPPs with dramatically improved ability to deliver cargoes to cells at low concentration. A CPP library containing 8192 tat/penetratin hybrid peptides coupled to an 18-residue PNA is screened using the HeLa pTRE-LucIVS2 splice correction reporter system. The daughter CPPs identified are one to two orders of magnitude more efficient than the parent sequences at delivery of PNA, and also deliver a dye cargo and an anionic peptide cargo. The significant increase in performance following a single iteration of SME demonstrates the power of this approach to peptide sequence optimization.

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Section: Discussionmentioning

confidence: 99%

Synthetic molecular evolution of hybrid cell penetrating peptides

2018

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“…The possibilities are endless, and depend on what the focus of the improvement is for each case. Bioinformatic algorithms integrated with machine learning, where the design is automatic through the properties chosen, taking into consideration AMP/ACP libraries of existing molecules, are considered the future method for their rational design (Tyagi et al, 2013 ; Lin et al, 2015 ).…”

Section: Peptides With Antimicrobial and Anticancer Activitymentioning

confidence: 99%

Peptides with Dual Antimicrobial and Anticancer Activities

et al. 2017

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In recent years, the number of people suffering from cancer and multi-resistant infections has increased, such that both diseases are already seen as current and future major causes of death. Moreover, chronic infections are one of the main causes of cancer, due to the instability in the immune system that allows cancer cells to proliferate. Likewise, the physical debility associated with cancer or with anticancer therapy itself often paves the way for opportunistic infections. It is urgent to develop new therapeutic methods, with higher efficiency and lower side effects. Antimicrobial peptides (AMPs) are found in the innate immune system of a wide range of organisms. Identified as the most promising alternative to conventional molecules used nowadays against infections, some of them have been shown to have dual activity, both as antimicrobial and anticancer peptides (ACPs). Highly cationic and amphipathic, they have demonstrated efficacy against both conditions, with the number of nature-driven or synthetically designed peptides increasing year by year. With similar properties, AMPs that can also act as ACPs are viewed as future chemotherapeutic drugs, with the advantage of low propensity to resistance, which started this paradigm in the pharmaceutical market. These peptides have already been described as molecules presenting killing mechanisms at the membrane level, but also acting toward intracellular targets, which increases their success compartively to one-target specific drugs. This review will approach the desirable characteristics of small peptides that demonstrated dual activity against microbial infections and cancer, as well as the peptides engaged in clinical trials.

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“…However, their impossibility to enter the cells has limited their therapeutic efficacy 6 . Sequence engineering of peptides and use of delivery systems as two well-known approaches are employed in order to improve ACP efficacy 7 8 . In the first approach, computational methods are used to design peptides with a higher anticancer activity 8 9 , while in delivery systems, various delivery vehicles, including cell penetration peptides (CPP), biopolymers and nanoparticles, have been developed to facilitate cellular uptake of pro-apoptotic peptides 5 9 10 11 .…”

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confidence: 99%

Tuning the anticancer activity of a novel pro-apoptotic peptide using gold nanoparticle platforms

Akrami

Balalaie

Hosseinkhani

et al. 2016

Sci Rep

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Pro-apoptotic peptides induce intrinsic apoptosis pathway in cancer cells. However, poor cellular penetration of the peptides is often associated with limited therapeutic efficacy. In this report, a series of peptide-gold nanoparticle platforms were developed to evaluate the anticancer activity of a novel alpha-lipoic acid-peptide conjugate, LA-WKRAKLAK, with respect to size and shape of nanoparticles. Gold nanoparticles (AuNPs) were found to enhance cell internalization as well as anticancer activity of the peptide conjugates. The smaller nanospheres showed a higher cytotoxicity, morphological change and cellular uptake compared to larger nanospheres and nanorods, whereas nanorods showed more hemolytic activity compared to nanospheres. The findings suggested that the anticancer and biological effects of the peptides induced by intrinsic apoptotic pathway were tuned by peptide-functionalized gold nanoparticles (P-AuNPs) as a function of their size and shape.

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Multidimensional Design of Anticancer Peptides

Cited by 35 publications

References 35 publications

Synthetic molecular evolution of hybrid cell penetrating peptides

Synthetic molecular evolution of hybrid cell penetrating peptides

Peptides with Dual Antimicrobial and Anticancer Activities

Tuning the anticancer activity of a novel pro-apoptotic peptide using gold nanoparticle platforms

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