Identification of multifunctional peptides from human milk

Mandal, Santi M.; Bharti, Rashmi; Porto, William F.; Gauri, Samiran S.; Mandal, Mahitosh; Franco, Octávio L.; Ghosh, Ananta K.

doi:10.1016/j.peptides.2014.03.017

Cited by 50 publications

(48 citation statements)

References 53 publications

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“…There are various other AMPs, in human milk, active in microbe killing, which can supplement the protection of the immature neonatal intestine (14, 65). hBD-1 is one example of an AMP in human milk, which affects pathogen membrane permeability and cytokine stimulation in the intestine (66).…”

Section: Innate Mechanisms Of Pathogen Recognitionmentioning

confidence: 99%

“…Many components in milk are multifunctional, serving as enzymes, antimicrobial proteins/peptides (AMPs), growth factors, chemokines, antioxidants, anti-inflammatory elements, prebiotics, probiotics, and nutrients for the growing infant (14, 15). The use of modern molecular approaches such as microbial genomics, metabolomics, proteomics, and glycomics has led to novel discoveries in both composition and function of human milk components.…”

Section: Introductionmentioning

confidence: 99%

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Innate Immunity and Breast Milk

2017

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Human milk is a dynamic source of nutrients and bioactive factors; unique in providing for the human infant’s optimal growth and development. The growing infant’s immune system has a number of developmental immune deficiencies placing the infant at increased risk of infection. This review focuses on how human milk directly contributes to the infant’s innate immunity. Remarkable new findings clarify the multifunctional nature of human milk bioactive components. New research techniques have expanded our understanding of the potential for human milk’s effect on the infant that will never be possible with milk formulas. Human milk microbiome directly shapes the infant’s intestinal microbiome, while the human milk oligosaccharides drive the growth of these microbes within the gut. New techniques such as genomics, metabolomics, proteomics, and glycomics are being used to describe this symbiotic relationship. An expanded role for antimicrobial proteins/peptides within human milk in innate immune protection is described. The unique milieu of enhanced immune protection with diminished inflammation results from a complex interaction of anti-inflammatory and antioxidative factors provided by human milk to the intestine. New data support the concept of mucosal-associated lymphoid tissue and its contribution to the cellular content of human milk. Human milk stem cells (hMSCs) have recently been discovered. Their direct role in the infant for repair and regeneration is being investigated. The existence of these hMSCs could prove to be an easily harvested source of multilineage stem cells for the study of cancer and tissue regeneration. As the infant’s gastrointestinal tract and immune system develop, there is a comparable transition in human milk over time to provide fewer immune factors and more calories and nutrients for growth. Each of these new findings opens the door to future studies of human milk and its effect on the innate immune system and the developing infant.

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Section: Innate Mechanisms Of Pathogen Recognitionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Innate Immunity and Breast Milk

2017

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“…[10,11] Bioactive peptides are commonly specific fragments of proteins that elicit biological activity and consequently modulate the health status of individuals. Some of the reported bioactivities elicited by bioactive peptides include antibacterial, [13][14][15] antifungal, [16] anti-inflammatory, [17,18] antioxidant, and angiotensin-converting enzyme (ACE) inhibitory activities. This is evident by the propensity of databases and repositories containing huge amount of data on bioactive peptide structure, properties, and activities.…”

Section: Introductionmentioning

confidence: 99%

Structural properties of bioactive peptides with α‐glucosidase inhibitory activity

et al. 2017

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Bioactive peptides are emerging as promising class of drugs that could serve as α-glucosidase inhibitors for the treatment of type 2 diabetes. This article identifies structural and physicochemical requirements for the design of therapeutically relevant α-glucosidase inhibitory peptides. So far, a total of 43 fully sequenced α-glucosidase inhibitory peptides have been reported and 13 of them had IC values several folds lower than acarbose. Analysis of the peptides indicates that the most potent peptides are tri- to hexapeptides with amino acids containing a hydroxyl or basic side chain at the N-terminal. The presence of proline within the chain and alanine or methionine at the C-terminal appears to be relevant for high activity. Hydrophobicity and isoelectric points are less important variables for α-glucosidase inhibition whilst a net charge of 0 or +1 was predicted for the highly active peptides. In silico simulated gastrointestinal digestion revealed that the high and moderately active peptides, including the most potent peptide (STYV), were gastrointestinally unstable, except SQSPA. Molecular docking of SQSPA, STYV, and STY (digestion fragment of STYV) with α-glucosidase suggested that their hydrogen bonding interactions and binding energies were comparable with acarbose. The identified criteria will facilitate the design of new peptide-derived α-glucosidase inhibitors.

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“…Furthermore, there is also evidence that CARPs activate pro-survival signaling pathways [67,94], modulate immune responses [95,96,97] and act as anti-oxidant molecules in their own right due to their guanidine group in arginine residues [65,83,98,99,100,101]. …”

Section: Neuroprotective Peptides and Their Therapeutic Applicatiomentioning

confidence: 99%

Perinatal Hypoxic-Ischemic Encephalopathy and Neuroprotective Peptide Therapies: A Case for Cationic Arginine-Rich Peptides (CARPs)

et al. 2018

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Perinatal hypoxic-ischemic encephalopathy (HIE) is the leading cause of mortality and morbidity in neonates, with survivors suffering significant neurological sequelae including cerebral palsy, epilepsy, intellectual disability and autism spectrum disorders. While hypothermia is used clinically to reduce neurological injury following HIE, it is only used for term infants (>36 weeks gestation) in tertiary hospitals and improves outcomes in only 30% of patients. For these reasons, a more effective and easily administrable pharmacological therapeutic agent, that can be used in combination with hypothermia or alone when hypothermia cannot be applied, is urgently needed to treat pre-term (≤36 weeks gestation) and term infants suffering HIE. Several recent studies have demonstrated that cationic arginine-rich peptides (CARPs), which include many cell-penetrating peptides [CPPs; e.g., transactivator of transcription (TAT) and poly-arginine-9 (R9; 9-mer of arginine)], possess intrinsic neuroprotective properties. For example, we have demonstrated that poly-arginine-18 (R18; 18-mer of arginine) and its D-enantiomer (R18D) are neuroprotective in vitro following neuronal excitotoxicity, and in vivo following perinatal hypoxia-ischemia (HI). In this paper, we review studies that have used CARPs and other peptides, including putative neuroprotective peptides fused to TAT, in animal models of perinatal HIE. We critically evaluate the evidence that supports our hypothesis that CARP neuroprotection is mediated by peptide arginine content and positive charge and that CARPs represent a novel potential therapeutic for HIE.

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Identification of multifunctional peptides from human milk

Cited by 50 publications

References 53 publications

Innate Immunity and Breast Milk

Innate Immunity and Breast Milk

Structural properties of bioactive peptides with α‐glucosidase inhibitory activity

Perinatal Hypoxic-Ischemic Encephalopathy and Neuroprotective Peptide Therapies: A Case for Cationic Arginine-Rich Peptides (CARPs)

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