**Bioactive Peptides from Algae: Traditional and Novel Generation Strategies, Structure-Function Relationships, and Bioinformatics as Predictive Tools for Bioactivity**

**Jack O'Connor 1,2, Marco Garcia-Vaquero 3,\*, Steve Meaney 1 and Brijesh Kumar Tiwari 2**

> 1 School of Biological & Health Sciences, Technological University Dublin, Dublin 2, Ireland; jack.oconnor@teagasc.ie (J.O.); steve.meaney@tudublin.ie (S.M.)


**Abstract:** Over the last decade, algae have been explored as alternative and sustainable protein sources for a balanced diet and more recently, as a potential source of algal-derived bioactive peptides with potential health benefits. This review will focus on the emerging processes for the generation and isolation of bioactive peptides or cryptides from algae, including: (1) pre-treatments of algae for the extraction of protein by physical and biochemical methods; and (2) methods for the generation of bioactive including enzymatic hydrolysis and other emerging methods. To date, the main biological properties of the peptides identified from algae, including anti-hypertensive, antioxidant and antiproliferative/cytotoxic effects (for this review, anti-proliferative/cytotoxic will be referred to by the term anti-cancer), assayed in vitro and/or in vivo, will also be summarized emphasizing the structure–function relationship and mechanism of action of these peptides. Moreover, the use of in silico methods, such as quantitative structural activity relationships (QSAR) and molecular docking for the identification of specific peptides of bioactive interest from hydrolysates will be described in detail together with the main challenges and opportunities to exploit algae as a source of bioactive peptides.

**Keywords:** in silico; biotechnology; cryptides; anti-hypertensive; antioxidant; anti-cancer
