什么样的顺序和结构性因素会影响小肽服用后的生物利用度? 哪些生理数据能确定肽被服用后是否进入到全身血液循环? 哪些模型能够用于评估肽的生物利用度? 这项任务是要求从相关的出版物，硅片模型和现有的研究数据中总结出有建设性的结论，提交一份书面建议书。 “征稿件请直接上传网址：https://www.innocentive.com” Understanding Bioavailability of Peptides TAGS: Nature, Global Health, Life Sciences, Food/Agriculture, Chemistry, Theoretical-licensing AWARD: $20,000 USD | DEADLINE: 1/09/13 | ACTIVE SOLVERS: 35 | POSTED: 11/09/12 What sequence and structural factors influence the bioavailability of small peptides following ingestion? Which physiological parameters determine whether peptides reach and persist in the systemic circulation, and which models would be relevant to assess peptide bioavailability? The Seeker is looking for insightful submissions that are supported by peer-reviewed publications, in-silico modelling &/or existing research data. This Challenge requires only a written proposal. Detailed Description & Requirements Background Hydrolysed milk proteins are used both in infant feeds and other food products. Either heat and pH or enzymatic processes are used to hydrolyze whey or casein proteins to smaller peptide species or single amino acids. These preparations contain peptides of 2-12 amino acids in length. While the mechanisms by which individual amino acids are absorbed and metabolized is well understood the knowledge about absorption mechanisms of peptides is much more limited. This Challenge requests in depth theoretical insights regarding which amino acid sequences or structures of casein-derived peptides and which physiological parameters are most influential in determining bioavailability. The focus is on bioavailability in human infants (0-2 years). Problem Bovine casein is a mix of AlphaS1, AlphaS2, Beta and Kappa-casein. Extensively hydrolysed casein contains a mixture of peptides 2-12 amino acids in length. Besides their established application in cow’s milk allergy, these casein hydrolysate derived peptides may have additional functionalities for human health in extra-intestinal tissues. These properties largely depend on their bioavailability and absorption characteristics as well as stability in plasma. Therefore, the main focus of this Challenge is whether these peptides can become systemically available intact – a prerequisite to exert bioactivity (in extra-intestinal tissues) related to specific health benefits. Well described physiological processes are known to result in digestion of proteins and peptides to individual amino acids, which are then taken up by the gut epithelium and from there into the blood stream. This digestive process and the uptake of amino acids is NOT the focus of the challenge. It is hypothesized that peptides from bovine casein hydrolysates can also become bioavailable from the gut, especially in infants in which the intestinal tract and the immune system are still developing. Which sequence motifs, or other characteristics of the casein-derived peptides influence their uptake from the gut lumen and subsequent systemic circulation? How could this be enhanced? Some critical parameters involved in this process may include, but are not limited to, peptide stability in the stomach and intestine, uptake by gut epithelia, transfer to the bloodstream and stability in plasma, resulting in distribution to other tissues. There is very limited evidence on transepithelial transport of casein-derived peptides and their systemic uptake into the blood, including e.g. measurements of plasma peptide concentrations after ingestion of a hydrolysate vs. the intact casein protein or detection of peptides in the apical/basal compartment. The Challenge The Seeker requires a comprehensive, evidence based understanding of the below questions: Which casein-derived peptides (2-12 amino acids long) can become systemically available intact after oral ingestion in infants (0-2 years)? Which properties of these peptides are crucial for their bioavailability and half-life in blood? Which physiological parameters during digestion, absorption and circulation determine whether peptides become systemically available? Which factors might increase peptide availability and stability in blood? What in-vitro or animal models and measurements are most useful in modeling systemic availability of small peptides in infant humans? It is likely that peptides of 2 – 12 amino acids may actively bind to and interfere with host cells. The Seeker is eager to predict the likelihood for uptake and gut-liver-blood passage, as well as systemic and central (brain) bioavailability of smaller peptides from an extensive casein hydrolysate. Exclusion criteria: The Seeker is NOT looking for information related to amino acid uptake and data related to the basic nutritional value of peptides as such. For possibilities to improve peptide availability and stability in blood, the Seeker is not interested in technologies such as encapsulation to improve gastrointestinal survival. Your proposal should fulfill the following Technical Requirements: The proposal should: Describe peptide structures, specific sequences or physicochemical parameters that are critical for systemic bioavailability of intact casein-derived peptides (2-12 amino acids in length) in human infants after oral intake.This proposal should be based on peer-reviewed literature, existing experimental data or in-silico assessments of bovine casein-derived peptides. Describe physiological parameters related to digestion, absorption and circulation that determine whether these intact peptides become systemically available and can be distributed to extra-intestinal tissues. Describe factors (such as supportive ingredients or technologies) that can support availability and systemic circulation of these intact peptides. Describe in silico, in-vitro or animal models and measurements that are relevant to better understanding bioavailabity of peptides ingested through the oral route. Animal or cell identity and genotypes/phenotypes should be disclosed as well as any proposed experimental protocols, end points and assay platforms / read out technologies. The seeker considers the following as ‘nice to have’: With regard to related health benefits, provide insights into bioactivity of casein hydrolysate derived peptides that can become systemically available. Project Criteria The submitted proposal should include the following: A comprehensive proposal that addresses each of the Technical Requirements listed above. Summary of the state of that art knowledge regarding the uptake and systemic distribution of casein hydrolysate derived peptides ingested through the oral route, including: Reference to peer-reviewed scientific literature or existing experimental data Reference to any in-vivo or in-vitro studies or in-silico predictive analyses. A description of your knowledge & expertise relevant to the challenge topic Your availability, in principle, to engaging with the Seeker in a contractual relationship The proposal should not include any personal identifying information (name, username, company, address, phone, email, personal website, resume, etc.) The Challenge award will be contingent upon theoretical evaluation of the proposal by the Seeker. To receive an award, the Solvers will not have to transfer their exclusive IP rights to the Seeker. Instead, they will grant to the Seeker non-exclusive license to practice their solutions.
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